![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 293, Issue 1, 196-205, April 2000
Department of Cardiac Physiology, National Cardiovascular Center
Research Institute, Suita, Osaka, Japan (H.K., M.Ya.); First Department
of Internal Medicine, Kobe University School of Medicine, Kobe, Japan
(H.K., M.Yo., H.A.); and Department of Pharmacology II, Faculty
of Medicine, Osaka University, Osaka, Japan (K.M., Y.K.)
Tertiapin is a 21-residue peptide isolated from honey bee
venoms. A recent study indicated that tertiapin is a potent blocker of
certain types of inwardly rectifying K+ (Kir) channels (Jin
and Lu, 1998). We examined the effect of tertiapin on ion channel
currents in rabbit cardiac myocytes using the patch-clamp technique. In
the whole-cell configuration, tertiapin fully inhibited acetylcholine
(1 µM)-induced muscarinic K+ (KACh) channel
currents in atrial myocytes with the half-maximum inhibitory
concentration of ~8 nM through ~1:1 stoichiometry. The potency of
tertiapin in inhibiting KACh channels was not significantly different at 
40 and 100 mV. Tertiapin also inhibited the
KACh channel preactivated by intracellular guanosine
5'-O-(3-thiotriphosphate), a nonhydrolyzable GTP analog.
A constitutively active Kir channel, the IK1 channel, was
at least 100 times less sensitive to tertiapin. Another Kir channel in
cardiac myocytes, the ATP-sensitive K+ channel, was
virtually insensitive to tertiapin (1 µM). The voltage-dependent K+ and the L-type Ca2+ channels
were not affected by tertiapin (1 µM). At the single-channel level,
tertiapin inhibited the KACh channel from the outside of the membrane by reducing the NPo (N is the number of
functional channels, and the Po is the open probability of
each channel) without affecting the single-channel conductance or fast
kinetics. Therefore, tertiapin potently and selectively blocks the
KACh channel in cardiac myocytes in a receptor- and
voltage-independent manner. Tertiapin is a novel pharmacological tool
to identify the functional role of the KACh channel in the
parasympathetic regulation of the heart beat.
This article has been cited by other articles:
|
|
 |
|
  M. B. Sattler, S. K. Williams, C. Neusch, M. Otto, J. R. Pehlke, M. Bahr, and R. Diem Flupirtine as Neuroprotective Add-On Therapy in Autoimmune Optic Neuritis Am. J. Pathol., November 1, 2008; 173(5): 1496 - 1507. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. Troncoso Brindeiro, R. W. Fallet, P. H. Lane, and P. K. Carmines Potassium channel contributions to afferent arteriolar tone in normal and diabetic rat kidney Am J Physiol Renal Physiol, July 1, 2008; 295(1): F171 - F178. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. K. Landeen, D. A. Dederko, C. S. Kondo, B. S. Hu, N. Aroonsakool, J. H. Haga, and W. R. Giles Mechanisms of the negative inotropic effects of sphingosine-1-phosphate on adult mouse ventricular myocytes Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H736 - H749. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Voigt, A. Maguy, Y.-H. Yeh, X. Qi, U. Ravens, D. Dobrev, and S. Nattel Changes in IK,ACh single-channel activity with atrial tachycardia remodelling in canine atrial cardiomyocytes Cardiovasc Res, January 1, 2008; 77(1): 35 - 43. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Mintert, L. I. Bosche, A. Rinne, M. Timpert, M.-C. Kienitz, L. Pott, and K. Bender Generation of a constitutive Na+-dependent inward-rectifier current in rat adult atrial myocytes by overexpression of Kir3.4 J. Physiol., November 15, 2007; 585(1): 3 - 13. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Mizuno, A. Kamiya, T. Kawada, T. Miyamoto, S. Shimizu, and M. Sugimachi Muscarinic potassium channels augment dynamic and static heart rate responses to vagal stimulation Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1564 - H1570. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Rubinstein, S. Peleg, S. Berlin, D. Brass, and N. Dascal G{alpha}i3 primes the G protein-activated K+ channels for activation by coexpressed Gbeta{gamma} in intact Xenopus oocytes J. Physiol., May 15, 2007; 581(1): 17 - 32. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T.-J. Cha, J. R. Ehrlich, D. Chartier, X.-Y. Qi, L. Xiao, and S. Nattel Kir3-Based Inward Rectifier Potassium Current: Potential Role in Atrial Tachycardia Remodeling Effects on Atrial Repolarization and Arrhythmias Circulation, April 11, 2006; 113(14): 1730 - 1737. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Dobrev, A. Friedrich, N. Voigt, N. Jost, E. Wettwer, T. Christ, M. Knaut, and U. Ravens The G Protein-Gated Potassium Current IK,ACh Is Constitutively Active in Patients With Chronic Atrial Fibrillation Circulation, December 13, 2005; 112(24): 3697 - 3706. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Kanjhan, E. J. Coulson, D. J. Adams, and M. C. Bellingham Tertiapin-Q Blocks Recombinant and Native Large Conductance K+ Channels in a Use-Dependent Manner J. Pharmacol. Exp. Ther., September 1, 2005; 314(3): 1353 - 1361. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Bender, M.-C. Wellner-Kienitz, L. I Bosche, A. Rinne, C. Beckmann, and L. Pott Acute desensitization of GIRK current in rat atrial myocytes is related to K+ current flow J. Physiol., December 1, 2004; 561(2): 471 - 483. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Ehrlich, T.-J. Cha, L. Zhang, D. Chartier, L. Villeneuve, T. E. Hebert, and S. Nattel Characterization of a hyperpolarization-activated time-dependent potassium current in canine cardiomyocytes from pulmonary vein myocardial sleeves and left atrium J. Physiol., June 1, 2004; 557(2): 583 - 597. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. J. Michel, J. M. Robillard, and L.-E. Trudeau Regulation of rat mesencephalic GABAergic neurones through muscarinic receptors J. Physiol., April 15, 2004; 556(2): 429 - 445. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. D. Chauhan, H. Nilsson, A. Ahluwalia, and A. J. Hobbs Release of C-type natriuretic peptide accounts for the biological activity of endothelium-derived hyperpolarizing factor PNAS, February 4, 2003; 100(3): 1426 - 1431. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. V. Kuzhikandathil and G. S. Oxford Classic D1 Dopamine Receptor Antagonist R-(+)-7-Chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH23390) Directly Inhibits G Protein-Coupled Inwardly Rectifying Potassium Channels Mol. Pharmacol., July 1, 2002; 62(1): 119 - 126. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Yamada The Role of Muscarinic K+ Channels in the Negative Chronotropic Effect of a Muscarinic Agonist J. Pharmacol. Exp. Ther., February 1, 2002; 300(2): 681 - 687. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
