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.
Fukuta
Hiroyasu
H
Department of Physiology, Nagoya City University Medical School, Mizuho-ku, Nagoya 467-8601, Japan.
Kito
Yoshihiko
Y
Suzuki
Hikaru
H
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001683:Biological Clocks / Q000502:physiology; D001896:Boron Compounds / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D003652:Decanoic Acids / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006168:Guinea Pigs; D006880:Hydroxy Acids / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism; D009130:Muscle, Smooth / Q000502:physiology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism; D011706:Pyloric Antrum / Q000502:physiology*; D012433:Ryanodine / Q000494:pharmacology; D014475:Uncoupling Agents / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D001896:Boron Compounds; D002614:Chelating Agents; D003652:Decanoic Acids; D006880:Hydroxy Acids; D007211:Indoles; D010726:Phosphodiesterase Inhibitors; D015221:Potassium Channels; D014475:Uncoupling Agents; D012433:Ryanodine; D002110:Caffeine; D004533:Egtazic Acid; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; C052853:5-hydroxydecanoic acid; C109986:2-aminoethoxydiphenyl borate; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D005905:Glyburide; D002118:Calcium; C000543:cyclopiazonic acid