Biophysical mechanisms underlying the paradoxical potentiation of the low-voltage activated calcium current in thalamocortical neurons: a modeling study

In thalamocortical neurons relaying sensory information, we recently described a phosphorylation mechanism that induces a marked increase in the amplitude of the low-voltage activated Ca 2þ current (T-type). Surprisingly, potentiation of the T-current closely depends on the state of the channel and is, therefore, both voltage-and ATP-dependent. Further analysis of the modification of channel activity induced by this regulation, and underlying the increase in the macroscopic current amplitude, requires a detailed study of the T-current biophysical properties that, unfortunately, might be constrained by the technical limitations of whole-cell recordings. Therefore, in the present study we have developed an alternative approach that is based on computational models of T-channel activity using Markov gating schemes. We show that both modifications in the activation kinetics of the channels and/or the existence of a second channel population with a conducting state conditioned by a phosphorylation step can explain the specific properties of T-currents that have been observed in thalamocortical neurons as a result of their ATP/voltage-dependent regulation. The flexibility in the T-type current behavior that is incorporated in these models might also help to unravel new roles for T-channels in shaping the different firing properties of thalamocortical neurons.