Spontaneous electrical activity and associated changes in calcium concentration in guinea-pig gastric smooth muscle.

Spontaneous electrical activity and internal Ca(2+) concentration ([Ca(2+)](i)) were measured simultaneously using conventional microelectrodes and fura-2 fluorescence, respectively, in isolated circular smooth muscle bundles of the guinea-pig gastric antrum. The smooth muscle bundles generated periodic slow potentials with accompanying spike potentials and associated transient increases in [Ca(2+)](i) (Ca(2+)-transients). Nifedipine abolished the spike potentials but not the slow potentials, and reduced the amplitude of associated Ca(2+)-transients. Caffeine, in the absence or presence of ryanodine, reduced resting [Ca(2+)](i) levels and abolished the slow potentials and associated Ca(2+)-transients. Depolarization elevated and hyperpolarization reduced resting [Ca(2+)](i) levels with associated changes in the frequency of slow potentials. The amplitude of Ca(2+)-transients changed in a bell-shaped manner with the membrane potential change. Slow potentials and associated Ca(2+)-transients were abolished if [Ca(2+)](i) levels were reduced by BAPTA-AM or if the internal Ca(2+) pump was inhibited by cyclopiazonic acid. 2-Aminoethoxy-diphenylborate (2-APB), a known inhibitor of inositol trisphosphate (IP(3))-mediated Ca(2+) release, also blocked slow potentials and Ca(2+)-transients. Carbonyl cyanide m-chlorophenyl hydrazone (CCCP), a mitochondrial protonophore, depolarized the membrane, elevated [Ca(2+)](i) levels and abolished slow potentials and Ca(2+)-transients. Inhibition of mitochondrial ATP-sensitive K(+) channels by glybenclamide and 5-hydroxydecanoic acid (5-HAD) abolished slow potentials and Ca(2+)-transients, without altering the smooth muscle [Ca(2+)](i). It is concluded that in antrum circular muscles, the frequency of slow potentials is correlated with the level of [Ca(2+)](i). The slow potential is coupled to release of Ca(2+) from an internal store, possibly through the activation of IP(3) receptors; this may be initiated by the activation of ATP-sensitive K(+) channels in mitochondria following Ca(2+) handling by mitochondria.