Vol. 294, Issue 2, 555-561, August 2000

Histamine Suppresses A-Type Potassium Current in Myenteric Neurons from Guinea Pig Small Intestine¹

Alexander M. Starodub and Jackie D. Wood

Department of Physiology and Cell Biology, College of Medicine and Public Health, The Ohio State University, Columbus, Ohio

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 (I_A). Histamine and the selective histamine H₂ receptor agonist, dimaprit, reduced the amplitude of I_A without affecting the slope factor for I_A steady-state inactivation curves. Suppression of I_A 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 suppressed I_A. The results are consistent with the hypothesis that suppression of I_A 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.