COMPARISON OF HETEROLOGOUSLY EXPRESSED HUMAN CARDIAC AND SKELETAL-MUSCLE SODIUM-CHANNELS

In this study we have expressed and characterized recombinant cardiac and skeletal muscle sodium channel a subunits in tsA-201 cells under i dentical experimental conditions. Unlike the Xenopus oocyte expression system, in tsA-201 cells (transformed human embryonic kidney) both ch annels seem to gate rapidly, as in native tissue. In general, hSkM1 ga ting seemed faster than hH1 both in terms of rate of inactivation and rate of recovery from inactivation as well as time to peak current, Th e midpoint of the steady-state inactivation curve was similar to 25 mV more negative for hH1 compared with hSkM1, In both isoforms, the stea dy-state channel availability relationships (''inactivation curves'') shifted toward more negative membrane potentials with time. The cardia c isoform showed a minimal shift in the activation curve as a function of time after whole-cell dialysis, whereas hSkM1 showed a continued a nd marked negative shift in the activation voltage dependence of chann el gating. This observation suggests that the mechanism underlying the shift in inactivation voltage dependence may be similar to the one th at is causing the shift in the activation voltage dependence in hSkM1 but that this is uncoupled in the cardiac isoform. These results demon strate the utility and limitations of measuring cardiac and skeletal m uscle recombinant Na+ channels in tsA-201 cells. This baseline charact erization will be useful for future investigations on channel mutants and pharmacology.