| 12595299 |
Ju YK, Allen DG: Early effects of metabolic inhibition on intracellular Ca2+ in toad pacemaker cells: involvement of Ca2+ stores. Am J Physiol Heart Circ Physiol. 2003 Apr;284(4):H1087-94. Epub 2002 Dec 5.
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. |
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