Components of pacemaker potentials recorded from the guinea pig stomach antrum

Abstract.

Pacemaker potentials recorded intracellularly from the guinea pig stomach consisted of initial primary and following plateau components. Inhibition of the internal Ca²⁺ store pump with cyclopiazonic acid depolarized the membrane and inhibited the plateau component of pacemaker potentials. 2-Aminoethoxydiphenyl borate (an inhibitor of IP₃-induced Ca²⁺ release) and carbonyl cyanide m-chlorophenyl-hydrazone (a mitochondrial protonophore) depolarized the membrane and abolished pacemaker potentials. Low [Ca²⁺]_o solution reduced the frequency and rate of rise of pacemaker potentials, and the effects were mimicked by BAPTA-AM (an intracellular Ca²⁺ chelator). 4,4′-Diisothiocyanatostilbene-2,2′-disulphonic acid and low [Cl^–]_o solution inhibited the plateau component of pacemaker potentials. Depolarization of the membrane with high [K⁺]_o solutions increased the frequency and reduced the dV/dt _max of pacemaker potentials. During high-[K⁺]_o-induced depolarization, cyclopiazonic acid abolished pacemaker potentials. Caffeine, forskolin, papaverine, 8-bromo-cGMP and (±)S-nitroso-N-acetylpenicillamine (SNAP) inhibited the plateau component, with no alteration of the primary component. It is concluded that the primary and plateau components of pacemaker potentials are related to voltage-gated Ca²⁺ influx and Ca²⁺-activated Cl^– channels, respectively, and cyclic nucleotides inhibit mainly the latter. Pacemaker potentials may be generated by the release of Ca²⁺ from internal stores through excitation of inositol 1,4,5-trisphosphate receptors, coupled with Ca²⁺ uptake into mitochondria.