No role for a voltage sensitive release mechanism in cardiac muscle.
We have investigated the possibility that some component of calcium release from the cardiac sarcoplasmic reticulum (SR) may occur directly in response to the surface membrane action potential rather than by calcium induced calcium release (CICR). Experiments were performed on rat ventricular myocytes and intracellular calcium concentration ([Ca(2+)](i)) measured with fluo-3. In order to mimic physiological conditions, experiments were performed at 37 degrees C, using the perforated patch technique (to avoid intracellular dialysis) with pulses from -80 to 0 mV. The addition of 500 microM Cd(2+) to inhibit the L-type Ca current reduced the rate of increase of the Ca transient to 2.8 +/- 1% of control. When experiments were performed with Na-free solutions in the pipette, Cd(2+) abolished the transient completely suggesting that the residual Ca entry was on Na-Ca exchange. The addition of Ni(2+) produced a concentration dependent inhibition of the Ca transient with 5 mM being sufficient to completely inhibit the transient. The inhibitory effects of Ni(2+) were unaffected by prior exposure to isoprenaline. These results provide no evidence for a voltage activated calcium release mechanism in cardiac muscle and are consistent with SR Ca(2+) release being triggered by a process of Ca(2+) induced Ca(2+) release.
Trafford
A W
AW
Unit of Cardiac Physiology, University of Manchester, 1.524 Stopford Building, Oxford Road, Manchester M13 9PT, UK. trafford@man.ac.uk
Eisner
D A
DA
D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology; D004553:Electric Conductivity; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D017136:Ion Transport; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology; D009532:Nickel / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D012519:Sarcoplasmic Reticulum / Q000502:physiology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D002104:Cadmium; D009532:Nickel; D000242:Cyclic AMP; D002118:Calcium