Regulation of Ca channel by intracellular Ca2+ and Mg2+ in frog ventricular cells.
The effects of changing the intracellular concentrations of Ca2+ or Mg2+ ([Ca2+]i, [Mg2+]i) on Ca current (ICa) was studied in frog ventricular myocytes using the whole-cell and cell-attached patch clamp techniques. In the physiological range of [Mg2+]i an increase in [Ca2+]i enhanced ICa whereas at lower [Mg2+]i ICa was suppressed. The increase in ICa caused by Ca2+ loading was not mediated by phosphorylation since the kinase inhibitors H-8 ¿N-[2-(methylamino)-ethyl]-5-isoquinolinesulphonamide dihydrochloride¿, staurosporine and KN-62 ¿1-[N,O-bis(5-isoquinolinesulphonyl)-N-methyl-1-tyrosyl]-4- phenylpiperizine¿ and a non-hydrolysable adenosine 5'-triphosphate analogue beta,gamma-methyleneadenosine 5'-triphosphate did not prevent the Ca2+-induced ICa increase. ICa was dramatically increased from 10+/-6 (n=4) to 71+/-7 nA/nF (n=4) when [Mg2+]i was lowered from 1.0 x 10(-3) to 1.0 x 10(-6) M at a [Ca2+]i of 10(-8) M. The concentration response relation for inhibition of Ca channels by [Mg2+]i is modulated by [Ca2+]i. To account for the experimental results it is postulated that competitive binding of Ca2+ or Mg2+ to the Ca channel accelerates the transition of the channel from an active to a silent mode. Single-channel recordings support this hypothesis. The regulation may have clinical relevance in cytoprotection during cardiac ischaemia.
Yamaoka
K
K
Department of Physiology, School of Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima 734, Japan.
Seyama
I
I
D000818:Animals; D001001:Anura; D001464:Barium / Q000378:metabolism; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006352:Heart Ventricles / Q000737:chemistry* / Q000166:cytology; D007473:Ion Channels / Q000502:physiology; D008274:Magnesium / Q000502:physiology*; D009206:Myocardium / Q000737:chemistry* / Q000166:cytology*; D010766:Phosphorylation / Q000187:drug effects; D012964:Sodium / Q000494:pharmacology
D015220:Calcium Channels; D007473:Ion Channels; D001464:Barium; D012964:Sodium; D008274:Magnesium; D002118:Calcium