Ca2+ release-induced inactivation of Ca2+ current in rat ventricular myocytes: evidence for local Ca2+ signalling.

摘要: 1. Inactivation of Ca2+ current (ICa) induced by release from sarcoplasmic reticulum (SR) was studied in single rat ventricular myocytes using whole-cell patch-clamp and indo-1 fluorescence measurement techniques. 2. Depolarizing pulses to 0 mV elicited large transients ICa with biexponential inactivation kinetics. Varying SR loading a 20 s pulse caffeine showed that the fast component dependent on magnitude release. 3. quantified, independently voltage entry, function termed fractional inhibition (FICa). The relation FICa had negative slope, resembling single-channel (iCa) rather than bell-shaped current-voltage (I-V) macroscopic transients. 4. Intracellular dialysis 10 mM EGTA (150 nM free [Ca2+]) no effect release, despite abolition cell contraction. Dialysis 3 or BAPTA (180 attenuated concentration-dependent manner, greater at positive potentials, consistent more effective buffering microdomains smaller iCa. 5. Spatial profiles [Ca2+] near an opened channel were simulated. reached submillimolar levels mouth channel, dropped steeply as radial distance increased. At any given higher potentials. radii significantly reduced BAPTA, but not EGTA. 6. In conclusion, distinctive dependence susceptibility release-induced slow buffers suggests process is mediated through local changes vicinity closely associated channels ryanodine receptors.