Abstract
The effects of the nitric oxide donor, S-nitrosoacetylpenicillamine (SNAP), were tested on cultured dissociated guinea pig celiac ganglion neurons using whole cell patch-clamp recordings. S-nitrosoacetylpenicillamine induced a concentration- and voltage-dependent inwardly directed shift in holding current (inward current shift) in 89% of neurons. The inward current shift was prevented by pre-treatment with the nitric oxide scavenger reduced hemoglobin and was abolished by intra- or extracellular cesium. The amplitude of the inward current shift was also sensitive to the extracellular potassium concentration. The S-nitrosoacetylpenicillamine-induced inward current shift was mediated by a decrease in calcium-dependent potassium currents (IAHPs); apamin (100 nM), charybdotoxin (10 nM) or tetraethylammonium (5 mM) reduced but did not abolish the amplitude of its inward current shift and a combination of apamin and tetraethylammonium abolished the S-nitrosoacetylpenicillamine-induced inward current response. In the presence of extracellular cobalt, SNAP produced an outward current that was concentration- and voltage-dependent, abolished by reduced hemoglobin and extracellular cesium and reduced by 4-AP (1 mM); in the absence of cobalt, 4-AP increased the SNAP-induced inward current shift. These data indicate that NO exerts dual opposing effects on neuronal potassium conductances, namely an inward current shift mediated through an inhibition of IAHP and induction of an outward current mediated by activation of the potassium delayed rectifier.
Footnotes
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Send reprint requests to: Dr. D. L. Kreulen, Department of Physiology, West Virginia University, School of Medicine, Morgantown, WV 26506-9229.
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↵1 This study was supported by a WVU-School of Medicine Research Grant to R.A.T., NIH HL59189 and WVU-School of Medicine Research Grants to D.L.K. and American Heart Association Grant WV-97–02-F to K.N.B.
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↵2 Current address: Gastroenterology Research - K7, Henry Ford Health Sciences Center, 2799 West Grand Boulevard, Detroit MI 48202.
- Abbreviations:
- SNAP
- S-nitrosoacetylpenicillamine
- NO
- nitric oxide
- IMG
- inferior mesenteric ganglion
- CG
- celiac ganglion
- DRG
- dorsal root ganglion
- VH
- membrane holding potential
- Em
- resting membrane potential
- Rin
- membrane input resistance
- TEA
- tetraethylammonium
- 4-AP
- 4-aminopyridine
- ATP
- adenosine 3′5′ triphosphate
- MEM
- minimal essential medium
- NOS-IR
- nitric oxide synthase-like immunoreactivity
- Received November 13, 1997.
- Accepted April 17, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
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