Modulation of the sarcolemmal L-type current by alteration in SR Ca2+ release

Modulation of the L-type current by sarcoplasmic reticulum (SR) Ca2+ releas e has been examined in patch-clamped mouse myotubes. Inhibition of SR Ca2release by inclusion of ryanodine in the internal solution shifted the half -activating voltage (V-0.5) of the L-type current from 1.1 +/- 2.1 to -7.7 +/- 1.7 mV. Ruthenium red in the internal solution shifted V-0.5 from 5.4 /- 1.9 to -3.2 +/- 4.1 mV. Chelation of myoplasmic Ca2+ with 1,2-bis(2-amin ophenoxy)ethane-N,N,N',N'-tetraacetic acid perfusion shifted V-0.5 from 4.4 +/- 1.7 to -3.5 +/- 3.3 mV and increased the peak current. Extracellular c affeine (1 mM), which should enhance SR Ca2+ release, significantly decreas ed the peak Ca2+ current. In low (0.1 mM) internal EGTA, myotube contractio n was abolished by internal perfusion with ryanodine or ruthenium red, wher eas addition of caffeine to the extracellular solution lowered the contract ile threshold, indicating that these modulators of SR Ca2+ release had the expected effects on contraction. Therefore, SR Ca2+ release appears to modu late the sarcolemmal L-type current, suggesting a retrograde communication from the SR to the sarcolemmal L-type channels in excitation-contraction co upling.