Ca2+ current activation rate correlates with alpha(1) subunit density

We report here that L-type Ca2+ channels activate rapidly in myotubes expressing current at high density and slowly in myotubes expressing current at low density. Partial block of the current in individual cells does not slow activation, indicating that Ca2+ influx does not link activation rate to current density. Activation rate is positively correlated with the density of gating charge (Q(max)) associated with the L-type Ca2+ channels. They range of values for Q(max), and the relationship between activation rate and Q(max), are similar for myotubes expressing native or recombinant L-type Ca2+ channels, whereas peak Ca2+ current density is similar to 3-fold higher for native channels. Taken together, these results suggest that Ca2+ channel density can govern activation kinetics. Our findings have important implications for studies of ion channel function because they suggest that biophysical properties can be significantly influenced by channel density, both in heterologous expression systems and in native tissues.