Differential discrimination of fast and slow synaptic waveforms by two low-voltage-activated calcium channels.
Electrophysiological analysis of human embryonic kidney 293 cells stably expressing recombinant channels was used to compare how the biophysical properties of the low-voltage-activated Ca(2+) channels encoded by the alpha(1G) (Ca(V)3.1) or alpha(1I) (Ca(V)3.3) subunits shape their responses to excitatory synaptic potentials. In medium containing 2 mM extracellular Ca(2+) standard current-voltage relationships demonstrated both channel types to be clearly low-voltage activated with significant slowly activating current responses being observed at -66 mV. At all test potentials examined, activation of Ca(V)3.3 was substantially slower than that of Ca(V)3.1. To probe how these different T-type channels might respond to excitatory postsynaptic potentials (EPSPs), mock EPSPs with different kinetic profiles were created from the sum of exponentials. These waveforms were then used as command templates in voltage-clamp experiments. Ca(V)3.1-mediated channels responded effectively to both rapidly decaying mock EPSPs and slowly decaying EPSPs. In contrast, Ca(V)3.3-mediated channels were poorly gated by rapidly decaying EPSPs but were effectively activated by the more prolonged synaptic response. When activated with mock EPSPs Ca(V)3.3-mediated currents were more resistant to steady-state depolarisation of the pre-stimulus holding potential. Ca(V)3.3 currents were also more resistant to repetitive application of prolonged EPSPs, which caused substantial inactivation of Ca(V)3.1-mediated currents. The addition of a single mock action potential to the peak of a rapidly decaying EPSP voltage-clamp template greatly enhanced the currents produced by either Ca(V)3.1 or Ca(V)3.3-expressing cells. This facilitatory effect was considerably greater for Ca(V)3.3-mediated channels. From these data we suggest that the slow activation kinetics of Ca(V)3.3-mediated T-type channels enable them to respond selectively to either slow or suprathreshold synaptic potentials.
Warre
R C H
RC
Neurology CEDD, Glaxo SmithKline, New Frontiers Science Park, Harlow, Essex CM19 5AW, UK.
McNaughton
N C L
NC
Randall
A D
AD
D000818:Animals; D002118:Calcium / Q000378:metabolism; D020747:Calcium Channels, T-Type / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D002478:Cells, Cultured; D002490:Central Nervous System / Q000378:metabolism*; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D008564:Membrane Potentials / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*
D020747:Calcium Channels, T-Type; D002118:Calcium