Multiple levels of the single L-type Ca2+ channel conductance in adult mammalian ventricular myocytes.

In cardiac muscle, Ca(2+) entry through the L-type Ca(2+) channel during excitation triggers Ca(2+) release from sarcoplasmic reticulum (SR) via the ryanodine receptor, causing muscle contraction. This Ca(2+) induced Ca(2+) release (CICR) is locally controlled by openings of the single L-type Ca(2+) channel that triggers the opening of ryanodine receptors located within the dyadic junction. The unitary current through the single Ca(2+) channel determines the open probability of the ryanodine receptors, and hence the efficacy of CICR. Here, we report findings of multiple conductance levels of L-type Ca(2+) channels in freshly isolated rat ventricular myocytes. When 10mM Ca(2+) was used in the pipette solution as the charge carrier in the cell-attached configuration, the most frequently occurring conductance levels are 6.9pS and 2.9pS. Three distinct conductance levels were also observed, although infrequently, in the same cell, corresponding to unitary currents of 0.33pA, 0.24pA, and 0.17pA upon depolarization to -10mV. In conclusion, our data demonstrate the existence of multiple single L-type Ca(2+) channel conductance levels in the adult mammalian ventricular myocytes with Ca(2+) as the charge carrier. The multiple conductance levels present heterogeneity in the Ca(2+) trigger signal strength at local dyadic junctions. The physiological significance of this heterogeneity on affecting the efficacy of CICR in the cardiac muscle is discussed.