Blockade of microglial Cav1.2 Cachannel exacerbates the symptoms in a Parkinson's disease model.

Abstract

Cav1.2 channels are an L-type voltage-dependent Cachannel, which is specifically blocked by calcium antagonists. Voltage-dependent Cachannels are generally considered to be functional only in excitable cells like neurons and muscle cells, but recently they have been reported to also be functional in non-excitable cells like microglia, which are key players in the innate immune system and have been shown to be involved in the pathophysiology of Parkinson's disease. Here, we show that Cav1.2 channels are expressed in microglia, and that calcium antagonists enhanced the neuroinflammatory M1 transition and inhibited neuroprotective M2 transition of microglia in vitro. Moreover, intensive degeneration of dopaminergic neurons and accompanying behavioural deficits were observed in microglia-specific Cav1.2 knockdown mice intoxicated with MPTP, a neurotoxin that induces Parkinson's disease-like symptoms, suggesting detrimental effects of microglial Cav1.2 blockade on Parkinson's disease. Therefore, microglial Cav1.2 channel may have neuroprotective roles under physiological conditions and may also contribute to recovery from disease conditions.