Voltage-dependent Ca²⁺ channels (Ca_V channels) are pivotal players in many physiological roles such as secretion, contraction, migration and excitation.¹

The voltage-dependent Ca²⁺ channels are composed of several subunits; α1, β, α2δ and γ. Ca_V channels were originally divided into six physiological types: L-, N-, P-, Q-, R-, and T-type.¹

The Ca_V2.3 (formerly named α1E) protein, forms the R-type channels. R-type channels are highly sensitive to both SNX-482 (#RTS-500) and NiCl₂. Ca_V2.3 channels were shown to mediate fast excitatory transmission in several synapses including the hippocampus.²

Ca_V2.3 channels can be modulated by the muscarinic G-protein coupled receptors. 

In HEK-293 cells, expressing Ca_V2.3 channels, the R-type channel was shown to be both facilitated and inhibited by m1 and m2 muscarinic receptors. However, inhibition was much weaker than facilitation for the m1 receptor, while for m2 receptors, inhibition was much more pronounced than activation.³

Facilitation and inhibition by the same receptors was probably exerted via different pathways as was indicated by their response to various inhibitors.³