Regulation by L-Type Calcium Channels of Endocytosis: An Overview

Juliana M. Rosa, Carmen Nanclares, Angela Orozco, Inés Colmena, Ricardo de Pascual, Antonio G. García, Luis Gandía

The exocytotic neurotransmitter release process is tightly coupled to the membrane retrieval (endocytosis) process since both are calcium-dependent processes. For instance, at the adrenal chromaffin cells, catecholamine release is regulated by Ca(2+) entry through L, N and PQ subtypes of voltage-dependent calcium channels (VDCC). The contribution of a given VDCC subtype to exocytosis may differ according to the animal species studied, with L channels contributing only about 20 % to the total Ca(2+) entry in bovine chromaffin cells. However, data from electrophysiological experiments with membrane capacitance measurements and fluorescence imaging with FM dyes indicate that Ca(2+) entry through the L-type channels seems to selectively regulate the endocytotic response after the application of a single depolarizing pulse to voltage-clamped bovine chromaffin cells. How do L-type channels control endocytosis remains to be fully clarified. By using specific antibodies against VDCC subtypes and endocytic proteins (i.e. dynamin and clathrin), it has been demonstrated that VDCC subtypes do not co-localise with these proteins. On the other hand, electrophysiological data suggest that the particular mode of sustained Ca(2+) entry through slow-inactivating L-type channels could be responsible for the activation of the endocytotic machinery. Here, we present an overview of the current understanding of the contribution of L-type channels during endocytosis.