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

Spontaneous electrical activity and internal Ca2+ concentration ([Ca2+](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 [Ca2+](i) (Ca2+-transients). Nifedipine abolished the spike potentials but not the slow potentials, and reduced the amplitude of associated Ca2+-transients. Caffeine, in the absence or presence of ryanodine, reduced resting [Ca2+], levels and abolished the slow potentials and associated Ca2+-transients. Depolarization elevated and hyperpolarization reduced resting [Ca2+](i) levels with associated changes in the frequency of slow potentials. The amplitude of Ca2+-transients changed in a bell-shaped manner with the membrane potential change. Slow potentials and associated Ca2+-transients were abolished if [Ca2+](i) levels were reduced by BAPTA-AM or if the internal Ca2+ pump was inhibited by cyclopiazonic acid. 2-Aminoethoxy-diphenylborate (2-APB), a known inhibitor of inositol trisphosphate UN-mediated Ca2+ release, also blocked slow potentials and Ca2+-transients. Carbonyl cyanide m-chlorophenyl hydrazone (CCCP), a mitochondrial protonophore, depolarized the membrane, elevated [Ca2+](i) levels and abolished slow potentials and Ca2+-transients. Inhibition of mitochondrial ATP-sensitive K+ channels by glybenclamide and 5-hydroxydecanoic acid (5-HAD) abolished slow potentials and Ca2+ transients, without altering the smooth muscle [Ca2+](i). It is concluded that in antrum circular muscles, the frequency of slow potentials is correlated with the level of [Ca2+](i). The slow potential is coupled to release of Ca2+ from an internal store, possibly through the activation Of IP3 receptors; this may be initiated by the activation of ATP-sensitive K+ channels in mitochondria following Ca2+ handling by mitochondria.