Role of protein kinase C in the excitatory action of cholinergic nerve stimulation on spontaneous activity of circular smooth muscle isolated from the guinea-pig stomach antrum.

Following inhibition of NO production with nitroarginine, circular muscle isolated from the guinea-pig gastric antrum generated periodic slow potentials and unitary potentials. Transmural nerve stimulation (TNS) during the interval between slow potentials evoked an apamin-sensitive inhibitory junction potential (IJP) followed by an atropine-sensitive depolarization; the latter was either a transient depolarization with enhanced generation of unitary potentials or a slow potential. After inhibition of unitary potentials and slow potentials with 1 mM caffeine, TNS evoked an IJP and subsequent cholinergic depolarization, the latter developing slowly and lasting for about 10 s. TNS was unable to elicit a slow potential until a certain period of time had elapsed following the cessation of a slow potential. The period during which TNS could not evoke slow potentials (termed the high-threshold period) was about 10 s, and this period was increased by chelerythrine and decreased by phorbol esters. It is concluded that cholinergic nerve-mediated excitation of gastric muscle involves the activation of protein kinase C (PKC), and that the high-threshold period, during which the generation of slow potentials by TNS is inhibited, may be a consequence of reduced activity of PKC.