Distinct kinetics of cloned T-type Ca2 + channels lead to differential Ca2 + entry and frequency-dependence during mock action potentials.

Voltage-dependent activity around the resting potential is determinant in neuronal physiology and participates in the definition of the firing pattern. Low-voltage-activated T-type Ca2 +  channels directly affect the membrane potential and control a number of secondary Ca2 + -dependent permeabilities. We have studied the ability of the cloned T-type channels (α1G,H,I) to carry Ca2 +  currents in response to mock action potentials. The relationship between the spike duration and the current amplitude is specific for each of the T-type channels, reflecting their individual kinetic properties. Typically the charge transfer increases with spike broadening, but the total Ca2 +  entry saturates at different spike durations according to the channel type: 4 ms for α1G; 7 ms for α1H; and >  10 ms for α1I channels. During bursts, currents are inhibited and/or transiently potentiated according to the α1 channel type, with larger effects at higher frequency. The inhibition may be induced by voltage-independent transitions toward inactivated states and/or channel inactivation through intermediate closed states. The potentiation is explained by an acceleration in the channel activation kinetics. Relatively fast inactivation and slow recovery limit the ability of α1G and α1H channels to respond to high frequency stimulation ( >  20 Hz). In contrast, the slow inactivation of α1I subunits allows these channels to continue participating in high frequency bursts (100 Hz). The biophysical properties of α1G, H and I channels will therefore dramatically modulate the effect of neuronal activities on Ca2 +  signalling.