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Vol. 297, Issue 1, 403-409, April 2001
Departments of Psychiatry and Behavioral Neurosciences and Pharmacology and the Cellular and Clinical Neurobiology Training Program, Wayne State University School of Medicine, Detroit, Michigan
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Abstract |
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 Top
 Abstract
 Introduction
Materials and Methods
Results
Discussion
References
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Previous studies have shown that 5-hydroxytryptamine (5-HT) can modulate the hyperpolarization-activated nonselective cation current (Ih) to elicit a membrane depolarization in neurons. However, the receptor subtype involved in this response remains controversial. In the accompanying study, we have identified a 5-HT7 receptor-mediated depolarization in the anterodorsal nucleus of the thalamus (ADn). In the present study, we have examined the possible role of Ih in mediating this 5-HT7 receptor-mediated depolarization. We used the blind tight-seal patch clamp technique to examine the ability of 5-HT to modulate Ih in the ADn. We found that 5-HT induced a shift in the voltage dependence of Ih to more depolarized potentials. The pharmacology of the receptor mediating this effect was consistent with that of a 5-HT7 receptor. Since the 5-HT7 receptor is coupled positively to adenylate cyclase, we examined the cAMP dependence of the 5-HT-induced modulation of Ih. Intracellular addition of cAMP mimicked and occluded the 5-HT response. Conversely, in the presence of the protein kinase inhibitors H-8 and staurosporine, ADn neurons still expressed a 5-HT-induced shift in the voltage dependence of Ih. These results suggest that 5-HT regulates Ih in the ADn through a cAMP-dependent but protein kinase A (PKA)-independent mechanism. To determine the contribution of Ih to the 5-HT7 receptor-mediated depolarization, we used the selective Ih blocker ZD7288. This compound greatly reduced the depolarizing response elicited by activation of 5-HT7 receptors. We conclude that 5-HT7 receptors depolarize ADn neurons primarily by increasing Ih through a cAMP-dependent, PKA-independent mechanism.
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Introduction |
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Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
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In
the accompanying article (Chapin and Andrade, 2001
), we reported that
activation of the 5-HT7 receptor elicits a
membrane depolarization and associated inward current in the
anterodorsal nucleus of the thalamus (ADn). In many cases, 5-HT-induced
depolarizations are elicited through modulation of the
hyperpolarization-activated nonselective cation current,
Ih (Bobker and Williams, 1989; Pape and
McCormick, 1989; Takahashi and Berger, 1990; Larkman and Kelly, 1992;
Spain, 1994; Cardenas et al., 1999). Therefore, we tested the
possibility that Ih may, at least in part,
mediate the depolarization elicited by 5-HT7 receptors.
Ih is a widely distributed nonselective cation
current that is activated on hyperpolarization and can display very
slow activation kinetics. Under physiological conditions,
Ih reverses at approximately 
20 to 30 mV
(Yanagihara and Irisawa, 1980; Takahashi and Berger et al., 1990; Li et
al., 1993) and activates at hyperpolarized potentials with
half-activation (V0.5) values ranging
from 92 mV (Larkman and Kelly, 1992) to 75 mV (Banks et al., 1993).
Its time constant for activation in a physiological preparation can be
slower than 2 s (Pape and McCormick, 1989).
Ih is also blocked by ZD7288 with reasonable
selectivity and this compound can be used to differentiate it from
other currents (BoSmith et al., 1993; Harris and Constanti, 1995). A
final characteristic of Ih is its regulation by
cAMP. Increased intracellular cAMP shifts the voltage dependence of
activation of Ih to more depolarized potentials
(DiFrancesco and Tortora, 1991) and, in some cases, increases its
maximal conductance (Tokimasa and Akasu, 1990; Accili et al., 1997).
Since under physiological conditions Ih is an
inward current, these effects result in a greater number of
Ih channels open at rest. This change becomes
manifested as a membrane depolarization.
Ih-mediated depolarizations signaled through cAMP
secondary to the activation of 5-HT receptors have been identified in
several brain regions, including thalamic geniculate nuclei (Pape and McCormick, 1989), the brainstem nucleus prepositus hyppoglossi (Bobker
and Williams, 1989), the medial nucleus of the trapezoid body (Banks et
al., 1993), the cerebral cortex (Spain, 1994), and facial and spinal
motor neurons (Takahashi and Berger, 1990; Larkman and Kelly, 1992).
However, the specific serotonin receptor subtype involved in these
responses remains controversial (Bobker and Williams, 1989; McCormick
and Pape, 1990; Takahashi and Berger, 1990; Larkman and Kelly, 1992).
Given the involvement of cAMP in regulating Ih,
it seems most likely that the receptor involved would belong to the
5-HT4, 5-HT6, or
5-HT7 subtypes. However, this conjecture has not
been rigorously tested.
In the preceding study, we identified a serotonin-induced depolarization in the ADn that is mediated by receptors of the 5-HT7 subtype. We hypothesized that part or all of this 5-HT7 receptor-mediated depolarization/inward current could be mediated by modulation of Ih in a cAMP-dependent manner. Therefore, in the present study, we first examined whether 5-HT regulated Ih in the ADn. We then tested for involvement of a 5-HT7 receptor in this response using a pharmacological approach. Finally, we directly examined the role of Ih in mediating the 5-HT7 receptor-induced inward current in this region. From the results of these experiments, we conclude that 5-HT7 receptors depolarize ADn neurons by regulating Ih through a cAMP-dependent, but PKA-independent, mechanism.
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Materials and Methods |
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Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
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The methods for preparation of brain slices and
electrophysiological recordings were essentially as outlined in the
accompanying article (Chapin and Andrade, 2001). To generate
Ih activation curves, cells were held at 40 mV.
Current-voltage relationships were generated by applying 4.0- to 5.6-s
long hyperpolarizing pulses every 10 to 20 s to increasingly
hyperpolarized steps (in 5-10 mV increments). Ih
was measured by subtracting the instantaneous current from the
steady-state current. The amplitude of Ih was normalized to the maximal value.
Data Analysis.
Data were analyzed using Origin 6.0 (Microcal
Software, Northampton, MA). The voltage activation curve for each cell
was fitted to the Boltzmann equation
(I/Imax = 1{1 + exp[(Vm
V0.5)
s
1]}1), where
I/Imax is the normalized current,
Vm is the command voltage, V0.5 is the half-activation voltage,
and s is the slope factor. The slope factors and the
V0.5 values were allowed to vary for analysis. Statistical data were tested using GB-STAT 6.0 or
GraphPad Prism. Fitting of the time constant of activation was
done using a second-order exponential decay equation (I = Io + A1e(xxo)/
1 + A2e(xxo)/2)
where I is the current, x represents time in ms,
and 
is the time constant. Except where indicated, data are
presented as means ± S.E.M.
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Results |
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Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
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As illustrated in Fig. 1A, cells of
the ADn express an Ih (n > 50 cells). We characterized this current by applying voltage steps to
increasingly hyperpolarized potentials from a holding potential of 40
mV (Fig. 1A). Steps to voltages negative to 60 mV revealed a slowly
developing inward relaxation. This is the physiological profile
expected for Ih. We confirmed that this slowly
developing inward current corresponded to Ih by
its sensitivity to ZD7288.
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Ih in the ADn displays many common
characteristics of this current found in other regions. We determined
the voltage activation of this current in the ADn by measuring
Ih at each voltage tested and normalizing these
to the greatest magnitude determined. We estimated the half-activation
(V0.5) of Ih by
fitting the data with the Boltzmann equation (see Materials and
Methods). The average V0.5 of
activation under control conditions was 81 ± 1.3 mV (Fig. 2, n = 12 cells).
Furthermore, the time constant of Ih activation increased with increasing hyperpolarization and could be fit by a
second-order exponential decay equation. These results are consistent with the properties of Ih seen in other studies
(Banks et al., 1993; Solomon and Nerbonne, 1993).
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We next examined the effect of bath application of 5-HT on the
activation curve for Ih. Bath application of 5-HT
(10 µM) induced an approximately 10 mV depolarizing shift in the
voltage dependence of activation of this current (Figs. 1 and 2). This
shift in the voltage dependence of activation is evident in the raw
traces as an increase in the amplitude of Ih at
more depolarized potentials (Fig. 1A). The
V0.5 for Ih in
the presence of serotonin (10 µM) was 71 ± 2.3 mV
(n = 7 cells). Thus, 5-HT increases
Ih at resting membrane potentials by shifting its
voltage dependence.
Pharmacology of the 5-HT-Induced Shift in the Voltage Dependence of
Ih Activation.
To test a
possible role for the 5-HT7 receptor subtype in
mediating the serotonin-induced shift in the voltage dependence of
Ih, we used agonists and antagonists capable of
distinguishing between serotonin receptor subtypes. One of the defining
characteristics of the 5-HT7 receptor is its
sensitivity to 5-carboxamidotryptamine (5-CT; Lovenberg et al.,
1993; Ruat et al., 1993). Therefore, we first tested the effects of
this compound on Ih. As illustrated in Fig. 2,
bath administration of 5-CT (3 µM) mimicked 5-HT and elicited a shift
in the voltage dependence of Ih
(V0.5 = 74 ± 1.5 mV,
n = 6 cells; t test, p < 0.01). A second pharmacological characteristic of the
5-HT7 receptor is its sensitivity to
8-hydroxydipropylaminotetralin (8-OHDPAT). This ligand has a high
affinity for the 5-HT1A receptor (Hoyer et al.,
1994) and a moderate affinity for the 5-HT6 and 5-HT7 receptors (Shen et al., 1993), yet has a
negligible affinity for most other serotonin receptor subtypes. Bath
application of 100 µM 8-OHDPAT to neurons of the ADn had no
detectable effect on the voltage dependence of
Ih, but effectively blocked the response to 5-HT
(n = 4 cells, ANOVA F = 0.14, p > 0.5 not shown). Finally, the
5-HT7 receptor also exhibits very high affinity
for LSD, a compound that appears to function as a low intrinsic
activity partial agonist when tested on 5-HT7
receptors expressed in heterologous systems (Ruat et al., 1993). Bath
administration of LSD (1 µM) had no detectable effect on the voltage
dependence of Ih, but blocked the effect of 5-HT
(n = 2 cells). These results exclude several 5-HT
receptor subtypes, including most 5-HT1
receptors, as well as receptors of the 5-HT2,
5-HT3, and 5-HT4 subtypes. As such, they are consistent with the possible involvement of a
receptor of the 5-HT7 subtype, but they do not
rule out the involvement of receptors of the
5-HT1A, 5-HT5, or
5-HT6 subtypes.
) and therefore can be used to distinguish
5-HT7 from 5-HT5 and
5-HT6 receptors. Cyanopindolol, in contrast,
exhibits high affinity for the 5-HT1A receptor,
but negligible affinity for receptors of the
5-HT7 subtype. Therefore, we next tested both of
these antagonists. Bath application of cyanopindolol (10 µM) by
itself had no detectable effect on the voltage dependence of Ih and failed to antagonize the effects of 5-HT
or 5-CT (Fig. 2, n = 4 cells). This failure was
unlikely to reflect inadequate penetration of cyanopindolol into the
slice because when administered at this same concentration to
hippocampal slices, under essentially identical recording conditions,
it readily inhibits 5-HT1A responses (Chapin and
Andrade, 2001). In contrast to the lack of effect of cyanopindolol,
bath administration of mesulergine (10 µM) completely blocked the
5-CT-induced shift in the voltage dependence of activation of
Ih (Fig. 3A). These
results are inconsistent with the involvement of
5-HT1A, 5-HT5, or
5-HT6 receptors and suggested the involvement of
a receptor of the 5-HT7 subtype. More definitive
characterization was performed using the selective
5-HT7 antagonist SB-269770. Bath administration
of this compound (1-10 µM) blocked the shift in the voltage
dependence of activation induced by 5-HT (Fig. 3B). This indicates that
5-HT modulates Ih through the
5-HT7 receptor subtype.
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Molecular Mechanism of the Shift in the Voltage Dependence of
Ih Activation.
Previous studies
have shown that 5-HT7 receptors couple to
stimulation of adenylate cyclase and the cAMP signaling pathway (Lovenberg et al., 1993; Meyerhof et al., 1993; Shen et al., 1993; Heidmann et al., 1998). Hence, a 5-HT7-mediated
response may be signaled by increases in cAMP. Therefore, we examined
the possible involvement of cAMP in signaling the effect of 5-HT in the
ADn. To test this possibility, we added 1 mM cAMP directly into the intracellular solution used for whole-cell recording. Intracellular perfusion of cAMP produced a large shift in the voltage dependence of
Ih (Fig. 4), such
that the V0.5 of
Ih under these conditions was shifted to 66.4
mV ± 1.8 mV (n = 4 cells tested). This value was
significantly different from the V0.5
obtained without cAMP in the intracellular recording solution (ANOVA,
F = 11.06, p < 0.001, control versus
cAMP, Tukey's post hoc test, p < 0.01). This shift in
voltage dependence was associated with a significant increase in
holding current at near-rest membrane potentials (60 to 70 mV; Fig.
4). Thus, cAMP mimics the effects of serotonin on
Ih in the ADn. This is consistent with the well
known regulation of Ih by cAMP (Bobker and
Williams, 1989; Pape and McCormick, 1989; DiFrancesco and
Tortora, 1991).
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) by binding to the channel
itself (Santoro et al., 2000), or indirectly via PKA through an
unidentified mechanism (Accili et al., 1997). To distinguish between
these two possibilities, we used the relatively broad-spectrum protein
kinase inhibitors staurosporine (1 µM) and H-8 (200 µM). To ensure
that the inhibitors would reach equilibrium, we preincubated the slices
with the inhibitors for 1 to 6 h before recording. These
experimental manipulations have been shown previously to be effective
in blocking PKA-mediated responses in brain slices (Chang et al., 1991,
1995; Torres et al. 1995). We found that staurosporine and H-8 both
failed to inhibit the ability of 5-HT to induced a shift in the voltage dependence of Ih (p > 0.5, Fig.
5). These results suggest that the 5-HT
shift in the voltage dependence of Ih does not
require activation of PKA in the ADn.
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The Role of Ih in the 5-HT7-Induced Inward
Current.
In the last set of experiments, we wished to ascertain
what role the modulation of Ih played in the
5-HT7 receptor-mediated inward current described
in the previous paper (Chapin and Andrade, 2001). To determine how much
of the 5-HT7-induced inward current is due to
modulation of Ih, we took advantage of the
selective Ih blocker ZD7288 (BoSmith et al.,
1993). As illustrated in Fig. 6A,
administration of ZD7288 (25-100 µM) greatly reduced, but did not
completely block, the 5-HT7 receptor-induced
inward current (Fig. 6). In a group of four cells tested using
this protocol, the modulation of Ih accounted for
71% ± 6% of the 5-HT-induced inward current (Fig. 7). The residual
5-HT7-induced inward current that remained after
ZD7288 was unlikely to be an effect on Ih since
ZD7288 completely blocked Ih measured using a
hyperpolarizing pulse (Fig. 6B, inset). From these experiments, we
conclude that an effect on Ih accounts for a
large fraction, but not all, of the 5-HT7-induced
inward current.
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Discussion |
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Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
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In the preceding study, we showed that 5-HT7 receptor stimulation induces a membrane depolarization and inward current in neurons of the ADn. In the present study, we examined the possibility that this inward current may result from a modulation of Ih. We found that 5-HT in the ADn shifts the voltage dependence of activation of Ih and that the pharmacology of the receptor mediating this effect has the characteristics of a 5-HT7 receptor. In addition, we found that, consistent with the involvement of a 5-HT7 receptor in this response, the effect on Ih is likely mediated via cAMP. Finally, we found that the selective Ih blocked ZD7822 greatly reduced the 5-HT7 receptor-mediated inward current seen in ADn neurons. Combined, these results suggest that 5-HT7 receptors signal a depolarization in the ADn primarily by increasing Ih through a cAMP-dependent mechanism.
Pharmacology of the 5-HT-Induced Modulation of Ih.
Previous studies in a variety of central neurons have described a
serotonin-induced depolarization mediated by an increase in
Ih (Bobker and Williams, 1989; Pape and
McCormick, 1989; Takahashi and Berger, 1990; Larkman and Kelly, 1992;
Spain, 1994). Many of these same studies have shown that this effect is
mediated through cAMP. Therefore, since 5-HT7
receptors are known to couple to G
s, it seemed
reasonable to hypothesize that Ih could mediate at least part of the 5-HT7-induced depolarization
in the ADn.
). Then, we examined whether serotonin regulated
Ih in the ADn. Bath administration of serotonin
increased Ih by shifting its voltage sensitivity in the depolarizing direction by approximately 10 mV. This effect is
similar to, albeit considerably larger than, that seen in other thalamic nuclei (Pape and McCormick, 1989).
Next, we examined whether the pharmacology of this effect on
Ih was consistent with the involvement of a
5-HT7 receptor. The ability of serotonin to shift
the voltage dependence of Ih was mimicked by 5-CT
and inhibited by 8-OHDPAT and LSD, whereas the effect of 5-CT was
antagonized by mesulergine, but not by cyanopindolol. This is the
pharmacological profile expected for a receptor of the
5-HT7 subtype. The only potential discrepancy is
that 8-OHDPAT and LSD have been reported to be partial agonists at the
5-HT7 receptor (Lovenberg et al., 1993; Ruat et
al., 1993), whereas they function as antagonists at the receptor
regulating Ih in the ADn. This discrepancy could
easily reflect differences in the strength of receptor G-protein
coupling. LSD exhibits very low intrinsic activity at 5-HT7
receptors even when heterologously expressed in Chinese Hamster ovary
cells (Ruat et al., 1993) and can be expected to function as an
antagonist in a more weakly coupled system. Similarly, 8-OHDPAT has
been reported to exhibit a reasonably high intrinsic activity when
tested in heterologous expression systems (50-90%; Lovenberg et al.,
1993; Plassat et al., 1993; Adham et al., 1998), but a lower intrinsic
activity when tested on natively expressed 5-HT7
receptors (Hirst et al., 1997; Thomas et al., 1999; Chapin and Andrade,
2001). If the 8-OHDPAT-induced shift in the
V0.5 of Ih was
similar in magnitude to its effect on the
5-HT7-induced inward current (approximately 20%
of the maximal 5-HT response), then the response would be below the
ability of our assay to detect agonist activity. As such, these results support the involvement of a 5-HT7 receptor in
mediating the effects of serotonin on Ih in the
ADn.
The results above exclude some receptors, most notably those of the
5-HT1, 5-HT2,
5-HT3, and 5-HT4 subtypes.
Furthermore, the effectiveness of mesulergine, which is more than
100-fold selective for the 5-HT7 receptor versus
5-HT5 and 5-HT6 (Hoyer et
al., 1994), strongly argues against the involvement of a receptor of
the 5-HT5 or 5-HT6 subtype.
Additional evidence supporting the involvement of
5-HT7 receptors in mediating the effect of 5-HT
on Ih was obtained with the selective
5-HT7 antagonist SB-269770 (Bacon and Beck, 2000;
Lovell et al., 2000), which blocked the 5-HT-induced response.
Unfortunately, the shift in voltage dependence of
Ih does not lend itself to the kind of
quantitative pharmacological analysis required for a definitive
receptor subtype identification. Therefore, we explored additional
avenues to test the possible involvement of 5-HT7
receptors in the regulation of Ih in the ADn.
Signal Transduction Mechanism of the 5-HT7-Induced
Shift in the Voltage Dependence of Activation of Ih.
Because the 5-HT7 receptor is coupled to
Gs and hence adenylate cyclase and cAMP
production (Adham et al., 1998), it seemed reasonable to expect that
responses signaled by a 5-HT7 receptor be
mediated via cAMP. In the present study, we found that cAMP can mimic
and occlude the serotonin-induced shift of the voltage activation of
Ih. This is consistent with a response that is
mediated through the cAMP-signaling cascade. This is in accord with
previous studies showing that cAMP can regulate
Ih (DiFrancesco and Tortora, 1991) and that
serotonin regulates Ih through cAMP in other
brain areas (Bobker and Williams, 1989; Pape and McCormick, 1989).
demonstrated that, in the heart, cAMP directly acts on the
Ih channel to shift the voltage dependence of
activation. This conclusion has been substantiated by the cloning of
four Ih channel subunits (HCN1-4), each
containing a cAMP binding domain in their sequence (Gauss et al., 1998;
Ludwig et al., 1998, 1999; Santoro et al., 1998). In addition, parallel
studies have shown that protein kinase inhibitors can reduce, and
protein phosphatase inhibitors can increase, the magnitude of
Ih current (Chang et al., 1991; Accili et al.,
1997). This modulation by phosphorylation seems to be different than the direct modulation by cAMP and may reflect the participation of HCN
channel subunits currently not cloned, or alternatively, a separate
means of modulation of Ih channels. Given these
two modes of regulation, we tested whether cAMP could be activating a
protein kinase, presumably PKA, to increase Ih.
To this effect, we used the kinase inhibitors H-8 and staurosporine.
These nonselective inhibitors would not allow us to identify the
protein kinase involved in the response, but a response that relies on
PKA activation should be blocked by these inhibitors (Chang et al.,
1991; Torres et al., 1995). In the present experiments, 5-HT could
still shift the voltage activation curve of Ih to
more depolarized potentials even in the presence of these inhibitors.
These results suggest that 5-HT modulates the Ih
current in the ADn through a cAMP-dependent, but PKA-independent,
mechanism. Similar conclusions have been reached by others working in
other regions of the brain (Bois et al., 1997; Larkman and Kelly,
1997).
Interestingly, 5-HT7 receptors have also been
recently reported to regulate calcium-activated potassium currents
(AHP) in the CA3 region of the hippocampus (Bacon and Beck, 2000). It
is known that cAMP and PKA mediates the ability of 5-HT to reduce the
AHP in the hippocampus (Torres et al., 1995). Thus, this suggests the
possibility that 5-HT7 receptors may signal their
effects in the brain through PKA-dependent and PKA-independent mechanisms.
Ih and the 5-HT7 Receptor-Mediated Inward Current. The above experiments suggested that serotonin increased Ih in the ADn through a cAMP-dependent mechanism, and that the receptor involved exhibited a pharmacological profile consistent with a 5-HT7 receptor. As such, these experiments suggested, but did not prove, that 5-HT7 receptors elicited a depolarization/inward current in the ADn by increasing Ih. To directly test this possibility, we used the selective Ih blocker ZD7822. Administration of this inhibitor reduced the 5-HT7 receptor-mediated inward current by about three-fourths. These results indicated that Ih channels carry a large proportion of the 5-HT7 receptor-induced inward current. Interestingly, a small residual current remained even after the Ih channels were blocked. This indicates that a second ionic mechanism may depolarize neurons of the ADn, but it is not clear whether this second component represents another receptor subtype or simply a second ionic mechanism by which the 5-HT7 receptor can alter cell properties. This uncertainty notwithstanding, the results outlined above identify the receptor signaling the increase in Ih in the ADn as belonging to the 5-HT7 subtype, and suggest that this effect on Ih accounts for most of the depolarization seen in the ADn in response to serotonin.
Serotonin has been shown previously to elicit a membrane depolarization by increasing Ih in a variety of neurons (Bobker and Williams, 1989; Pape and McCormick, 1989; Takahashi and Berger, 1990; Larkman and Kelly, 1992; Spain, 1994; Cardenas et al., 1999). However, the serotonin receptor subtype responsible for these actions
has remained controversial. In most of these studies, the receptor has
been reported to resemble the 5-HT1 subtype, although a more recent study on dorsal root ganglion cells has also
suggested the possible involvement of a 5-HT7
receptor (Cardenas et al., 1999). Such discrepancies are perhaps not
unexpected, given the complex pharmacology of the
5-HT7 receptor. In the present study, we have
used several distinct approaches to identify the receptor regulating
Ih in the ADn. These approaches converge in identifying the serotonin receptor regulating Ih
in the ADn as belonging to the 5-HT7 subtype.
Admittedly, it is difficult to extrapolate with certitude from the ADn
to other brain areas. However, these results nevertheless suggest that
the "orphan" serotonin receptor regulating Ih
in the brain corresponds to the 5-HT7 receptor.
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Acknowledgment |
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We thank Dr. S. Haj-Dahmane for advice on the experiments.
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Footnotes |
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Accepted for publication December 20, 2000.
Received for publication September 14, 2000.
This work was supported in part by a research grant (Joe Young, Sr.) from the State of Michigan and by Grant MH43985 from the National Institute of Mental Health.
Send reprint requests to: Dr. Rodrigo Andrade, Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, 2309 Scott Hall, Detroit, MI 48201. E-mail: randrade{at}med.wayne.edu
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Abbreviations |
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5-HT, 5-hydroxytryptamine; ADn, anterior dorsal nucleus of the thalamus; Ih, hyperpolarization-activated nonselective cation current; 5-CT, 5-carboxamidotryptamine; 8-OHDPAT, 8-hydroxydipropylaminotetralin; PKA, protein kinase A.
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References |
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Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
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, controls (n = 7 cells for 5-HT
and n = 6 cells for 5-CT); 
, 5-HT
(n = 7 cells); and 
5-CT (n = 6 cells). Error bars represent the S.E.M.
, control (n = 7 cells); 
, 5-HT (n = 7 cells); and 
