Subthreshold membrane potential oscillations in inferior olive neurons are dynamically regulated by P/Q- and T-type calcium channels: a study in mutant mice.
The role of P/Q- 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 used. 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.
Choi
Soonwook
S
New York University School of Medicine, Department of Physiology & Neuroscience, 550 First Ave, MSB 442, New York, NY 10016, USA.
Yu
Eunah
E
Kim
Daesoo
D
Urbano
Francisco J
FJ
Makarenko
Vladimir
V
Shin
Hee-Sup
HS
Llinás
Rodolfo R
RR
D000818:Animals; D020864:Calcium Channels, N-Type; D020865:Calcium Channels, P-Type / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D020907:Calcium Channels, Q-Type / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D020747:Calcium Channels, T-Type / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D020013:Calcium Signaling; D003198:Computer Simulation; D007700:Kinetics; D008564:Membrane Potentials; D051379:Mice; D018345:Mice, Knockout; D008959:Models, Neurological; D009474:Neurons / Q000378:metabolism*; D009847:Olivary Nucleus / Q000166:cytology / Q000378:metabolism*
D020864:Calcium Channels, N-Type; D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type; D020747:Calcium Channels, T-Type; C498197:Cacna1g protein, mouse