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 ([Ca2+](i)) measured with fluo-3. In order to mimic physiological conditions, experiments were performed at 37 degreesC, using the perforated patch technique (to avoid intracellular dialysis) with pulses from -80 to 0 mV. The addition of 500 muM Cd2+ 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, Cd2+ abolished the transient completely suggesting that the residual Ca entry was on Na-Ca exchange. The addition of Ni2+ produced a concentration dependent inhibition of the Ca transient with 5 MM being sufficient to completely inhibit the transient. The inhibitory effects of Ni2+ 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 Ca2+ release being triggered by a process of Ca2+ induced Ca2+ release. (C) 2003 Elsevier Science Ltd. All rights reserved.