The cloned cardiac Na channel alpha-subunit expressed in Xenopus oocytes show gating and blocking properties of native channels

Abstract

The neonatal rat cardiac Na channel alpha-subunit directed currents in oocytes show characteristic cardiac relative resistance to tetrodotoxin (TTX) block. TTX-sensitive currents obtained by expression in Xenopus oocytes of the alpha-subunits of the rat brain (BrnIIa) and adult skeletal muscle (microI) Na channels show abnormally slow decay kinetics. In order to determine if currents directed by the cardiac alpha-subunit (RHI) exhibit kinetics in oocytes like native currents, we compared RHI-directed currents in oocytes to Na currents in freshly isolated neonatal rat myocytes. The decay rate of RHI currents approached that of neonatal myocytes and was faster than BrnIIa and microI currents in oocytes. The voltage dependence of availability and activation was the same as that in the rat myocytes except for a 12-19 mV shift in the depolarizing direction. The RHI Na currents were sensitive to Cd2+ block, and they showed use dependence of TTX and lidocaine block similar to native currents. The current expressed in oocytes following injection of the cRNA encoding for the alpha-subunit of the cardiac Na channel possesses most of the characteristic kinetic and pharmacological properties of the native cardiac Na current.