The Gating and Conductance Properties of CaV3.2 Low-Voltage-Activated T-Type Calcium Channels.

Abstract

Calcium channels are essential for excitation-contraction coupling and pacemaker potentials in cardiac muscle cells. Whereas L-type Ca(2+) channels have been extensively studied, T-type channels have been poorly characterized in cardiac myocytes. We describe here the functional properties of recombinant Ca(V)3.2 T-type Ca(2+) channels expressed in mammalian cell lines. The T-type Ca(2+) current showed a rapid activation and an inactivation phase in response to depolarization, and it displayed a window current over the voltage range from -60 to -40 mV in 1 to 10 mM external Ca(2+). Barium (Ba(2+)) and strontium (Sr(2+)) permeate the channel with similar activation kinetics. On the other hand, monovalent cations, Li(+) and Na(+), permeate the T-type Ca(2+) channel more easily than the L-type Ca(2+) channel. The permeability order of the Ca(V)3.2 T-type Ca(2+) channel among monovalent and divalent cations was determined as Ba(2+)>Mn(2+)>Ca(2+)>Sr(2+)>Li(+1)>Na(+) with the permeability order of 1.39:1.25:1.00:0.95:0.55:0.29. The ionic conductance sequence for cations relative to calcium was Sr(2+)>Ba(2+)>Ca(2+)>Li(+1)>Mn(2+)>Na(+) with the conductance ratio of 1.39:1.21:1.00:0.40:0.23:0.11. The permeation profile of manganese (Mn(2+)) is complex. Mn(2+) permeates the Ca(2+) channel with a permeability similar to Ca(2+) or Ba(2+), but with a much smaller current density, resulting in a much smaller conductance. The properties relating to progression and recovery from inactivation in the Ca(V)3.2 channel are substantially identical with either Ca(2+) or Ba(2+) as the charge carrier.