Early effects of metabolic inhibition on intracellular Ca2+ in toad pacemaker cells: involvement of Ca2+ stores.
The early effects of metabolic inhibition on intracellular Ca(2+) concentration ([Ca(2+)](i)), Ca(2+) current, and sarcoplasmic reticulum (SR) Ca(2+) content were studied in single pacemaker cells from the sinus venosus of the cane toad. The amplitude of the spontaneous elevations of systolic [Ca(2+)](i) (Ca(2+) transients) was reduced after 5-min exposure to 2 mM NaCN from 338 +/- 30 to 189 +/- 37 nM (P < 0.005, n = 9), and the spontaneous firing rate was reduced from 27 +/- 2 to 12 +/- 4 beats/min (P < 0.002, n = 9). It has been proposed that CN(-) acts by inhibition of cytochrome P-450, resulting in a reduction of cAMP and Ca(2+) current. To test this proposal, we used clotrimazole, a cytochrome P-450 inhibitor, which also decreased the Ca(2+) transients and firing rate. CN(-) caused an insignificant fall of Ca(2+) current (23 +/- 11%) but a substantial reduction of SR Ca(2+) content (by 65 +/- 5%), whereas clotrimazole produced a larger reduction of Ca(2+) current and did not affect the SR Ca(2+) content. Thus the main effect of CN(-) does not seem to be through inhibition of cytochrome P-450. In conclusion, CN(-) appears to reduce Ca(2+) release from the SR mainly by reducing SR Ca(2+) content. A likely cause of the decreased SR content is reduced Ca(2+) uptake by the SR pump.
Ju
Yue-Kun
YK
Department of Physiology and Institute for Biomedical Research, University of Sydney, New South Wales 2006, Australia.
Allen
David G
DG
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002024:Bufo marinus / Q000502:physiology*; D002118:Calcium / Q000032:analysis / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D002319:Cardiovascular System / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D003022:Clotrimazole / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D065607:Cytochrome P-450 Enzyme Inhibitors; D004553:Electric Conductivity; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006339:Heart Rate; D010766:Phosphorylation; D012519:Sarcoplasmic Reticulum / Q000737:chemistry / Q000378:metabolism; D012966:Sodium Cyanide / Q000494:pharmacology*
D015220:Calcium Channels; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D003994:Bucladesine; D000242:Cyclic AMP; D003022:Clotrimazole; D012966:Sodium Cyanide; D002118:Calcium