T-type channel-mediated neurotransmitter release

Besides controlling awide variety of cell functions, T-type channels have been shown to regulate neurotransmitter release in peripheral and central synapses and neuroendocrine cells. Growing evidence over the last 10 years suggests a key role of Cav3.2 and Cav3.1 channels in controlling basal neurosecretion near resting conditions and sustained release during mild stimulations. In some cases, the contribution of low-voltage-activated (LVA) channels is not directly evident but requires either the activation of coupled presynaptic re- ceptors, block of ion channels, or chelation of metal ions. Concerning the coupling to the secretory machinery, T-type channels appear loosely coupled to neurotransmitter and hor- mone release. In neurons,Cav3.2 andCav3.1 channelsmainly control the asynchronous appearance of “minis” [miniature inhibitory postsynaptic currents (mIPSCs) and miniature ex- citatory postsynaptic currents (mEPSCs)]. The same loose coupling is evident frommembrane capacity and amperomet- ric recordings in chromaffin cells andmelanotropeswhere the low-threshold-driven exocytosis possesses the same linear Ca2+ dependence of the other voltage-gated Ca2+ channels (Cav1 and Cav2) that is strongly attenuated by slow calcium buffers. The intriguing issue is that, despite not expressing a consensus “synprint” site, Cav3.2 channels do interact with syntaxin 1A and SNAP-25 and, thus,may form nanodomains with secretory vesicles that can be regulated at low voltages. In this review, we discuss all the past and recent issues related to T-type channel-secretion coupling in neurons and neuroen- docrine cells.