Abstract
Perforated patch-clamp methods for recording ionic currents in the whole-cell configuration were used to test the hypothesis that the ionic mechanisms for the excitatory actions of histamine on enteric neurons include suppression of A-type K+ current (IA). Histamine and the selective histamine H2 receptor agonist, dimaprit, reduced the amplitude ofIA without affecting the slope factor forIA steady-state inactivation curves. Suppression of IA was restricted to after hyperpolarization-type myenteric neurons that were immunoreactive for calbindin. The selective histamine H2 receptor antagonist cimetidine suppressed the action of histamine and dimaprit. Elevation of intraneuronal cAMP by forskolin, a membrane-permeant analog of cAMP, and treatment with a phosphodiesterase inhibitor suppressedIA. The results are consistent with the hypothesis that suppression of IA is part of the ionic mechanism responsible for elevation of excitability during both slow synaptic excitation and slow synaptic excitation-like responses evoked by paracrine mediators, such as histamine, in after hyperpolarization-type myenteric neurons.
Footnotes
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Send reprint requests to: Jackie D. Wood, Ph.D., Department of Physiology and Cell Biology, 302 Hamilton Hall, 1645 Neil Ave., Columbus, OH 43210-1218. E-mail: wood.13{at}osu.edu
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↵1 This work was supported by National Institutes of Health Grant 1 RO1 DK46941 to J.D.W.
- Abbreviations:
- ENS
- enteric nervous system
- 4-AP
- 4-aminopyridine
- IA
- A-type K+current
- AH
- after hyperpolarization
- IBMX
- 3-isobutyl-1- methylxanthine
- sEPSP
- slow excitatory postsynaptic potential
- CPTcAMP
- 8-(4-chlorophenylthio) cAMP
- Received January 27, 2000.
- Accepted May 2, 2000.
- The American Society for Pharmacology and Experimental Therapeutics
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