Components of pacemaker potentials recorded from the guinea pig stomach antrum.
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.
Kito
Yoshihiko
Y
Department of Physiology, Nagoya City University Medical School, Mizuho-ku, Nagoya 467-8601, Japan.
Fukuta
Hiroyasu
H
Suzuki
Hikaru
H
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000818:Animals; D001683:Biological Clocks / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D002712:Chlorides / Q000008:administration & dosage; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D008297:Male; D009130:Muscle, Smooth / Q000502:physiology; D009994:Osmolar Concentration; D011188:Potassium / Q000378:metabolism; D011706:Pyloric Antrum / Q000502:physiology*; D012996:Solutions / Q000494:pharmacology
D002712:Chlorides; D012996:Solutions; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D000242:Cyclic AMP; D006152:Cyclic GMP; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D011188:Potassium; D002118:Calcium