T-type channels-secretion coupling: evidence for a fast low-threshold exocytosis

Abstract

T-type channels are transient low-voltage-activated (LVA) Ca(2+) channels that control Ca(2+) entry in excitable cells during small depolarizations around resting potential. Studies in the past 20 years focused on the biophysical, physiological, and molecular characterization of T-type channels in most tissues. This led to a well-defined picture of the functional role of LVA channels in controlling low-threshold spikes, oscillatory cell activity, muscle contraction, hormone release, cell growth and differentiation. So far, little attention has been devoted to the role of T-type channels in transmitter release, which mainly involves channel types belonging to the high-voltage-activated (HVA) Ca(2+) channel family. However, evidence is accumulating in favor of a unique participation of T-type channels in fast transmitter release. Clear data are now reported in reciprocal synapses of the retina and olfactory bulb, synaptic contacts between primary afferent and second order nociceptive neurons, rhythmic inhibitory interneurons of invertebrates and clonal cell lines transfected with recombinant alpha(1) channel subunits. T-type channels also regulate the large dense-core vesicle release of neuroendocrine cells where Ca(2+) dependence, rate of vesicle release, and size of readily releasable pool appear comparable to those associated to HVA channels. This suggests that when sufficiently expressed and properly located near the release zones, T-type channels can trigger fast low-threshold secretion. In this study, we will review the main findings that assign a specific task to T-type channels in fast exocytosis, discussing their possible involvement in the control of the Ca(2+)-dependent processes regulating exocytosis like vesicle depletion and vesicle recycling.