Subthreshold membrane potential oscillations in inferior olive neurons are dynamically regulated by P/Q and T calcium channels: A study in mutant mice.

CHOI S; YU E; KIM D; URBANO FJ; MAKARENKO V; SHIN HS; LLINAS RR

THE JOURNAL OF PHYSIOLOGY

WILEY-BLACKWELL PUBLISHING, INC

Año: 2010 vol. 588 p. 3031 - 3043

0022-3751

The role of P/Q-type and T-type calcium channels in the rhythmic oscillatory behaviour of inferior olive (IO) neurons was investigated in mutant mice. Mice lacking either the CaV2.1 gene of the pore-forming alpha1A subunit for P/Q-type calcium channel, or the CaV3.1, gene of the pore-forming alpha1G subunit for T-type calcium channel were utilized. In vitro intracellular recording from IO neurons reveals that the amplitude and frequency of sinusoidal subthreshold oscillations (SSTOs) were reduced in the CaV2.1-/- mice. In the CaV3.1-/- mice, IO neurons also showed altered patterns of SSTOs and the probability of SSTO generation was significantly lower (15 %, 5 of 34 neurons) than that of wild-type (78%, 31 of 40 neurons) or CaV2.1-/- mice (73%, 22 of 30 neurons). In addition, the low-threshold calcium spike and the sustained endogenous oscillation following rebound potentials were absent in IO neurons from CaV3.1-/- mice. Moreover, the phase-reset dynamics of oscillatory properties of single neurons and neuronal clusters in IO were remarkably altered in both CaV2.1-/- and CaV3.1-/- mice. These results suggest that both alpha1A P/Q- and alpha1G T-type calcium channels are required for the dynamic control of neuronal oscillations in the IO. These findings were supported by results from a mathematical IO neuronal model that incorporated T and P/Q channel kinetics.