Factors modifying the frequency of spontaneous activity in gastric muscle

Abstract

The cellular mechanisms that determine the frequency of spontaneous activity were investigated in gastric smooth muscles isolated from the guinea-pig. Intact antral muscle generated slow waves periodically; the interval between slow waves was decreased exponentially by depolarization of the membrane to reach a steady interval value of about 7 s. Isolated circular muscle bundles produced slow potentials spontaneously or were evoked by depolarizing current stimuli. Evoked slow potentials appeared in an all-or-none fashion, with a refractory period of approximately 2-3 s. Low concentrations of chemicals that modify intracellular signalling revealed that the refractory period was causally related to the activity of protein kinase C (PKC). Activation of PKC increased and inhibition of PKC activity decreased the frequency of slow potentials. Chemicals that inhibit mitochondrial functions reduced the frequency of slow waves. Inhibition of internal Ca(2+)-store activity decreased the amplitude, but not the frequency of slow potentials, suggesting that the amplitude is causally related to Ca(2+) release from the internal store. The results suggest that changes in [Ca(2+)](i) caused by the activity of mitochondria may play a key role in determining the frequency of spontaneous activity in gastric pacemaker cells.