Role of T-type calcium channel on tremorogenesis

Abstract

Tremor is a rhythmic muscle contraction that has been implicated in physiological and pathological functions of brain; however, the neural pacemaker underlying tremor rhythm remains obscure. Here, we investigate the role of T-type calcium channel on tremorogenesis, by using two models of essential tremor and mice lacking CaV3.1 T-type calcium channel. In harmaline-induced tremor model, potentiation of CaV3.1 is critical on the generation of 4-10Hz tremor rhythm in the inferior olive. In GABA-A α1 subunit knockout tremor model, however, absence of CaV3.1 enhances tremor by inducing 20-25Hz tremor-related oscillation in motor cortex; thus, T-type calcium channel is critical for pacemaking tremor rhythm and its way of contribution depends on the acting brain area. Our findings cast light on the molecular mechanism of tremorogenesis, proposing T-type calcium channel as a new therapeutic target of essential tremor.