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

Abstract

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.

L-Type Calcium Channel Blocker Enhances Cellular Delivery and Gene Silencing Potency of Cell-Penetrating Asymmetric siRNAs

“…Altogether, our results suggest that L-type CCBs may enhance the cellular internalization of cp-asiRNAs. These results correlated with previous findings suggesting that the inactive state of the L-type calcium channel stimulates endocytosis by sustaining membrane depolarizations for a longer time. , …”

“…In contrast, the T-type calcium channel blockers, penfluridol and ethosuximide, failed to enhance the cp-asiRNA activity, possibly due to the absence of key features associated with L-type CCBs. Consistent with this idea, it has been reported that DHP L-type calcium channel antagonists stabilize and inactivate L-type calcium channels and the slow inactivation of the persistent and lasting (L-type) calcium channel was related to endocytosis. , …”

“…Consistent with this idea, it has been reported that DHP L-type calcium channel antagonists stabilize and inactivate L-type calcium channels 42 and the slow inactivation of the persistent and lasting (L-type) calcium channel was related to endocytosis. 39,43 With regard to the IC 50 values of L-type CCBs provided in the results section, it appears that the concentration required to obtain an effect (Figure 2) is beyond the IC 50 values. Only amlodipine might be useful based on this consideration, where the physiology might be affected to an acceptable degree.…”

“…These results correlated with previous findings suggesting that the inactive state of the L-type calcium channel stimulates endocytosis by sustaining membrane depolarizations for a longer time. 38,39 As L-type CCBs improved cellular delivery of cp-asiRNAs, the endocytosis pathway of cp-asiRNAs was examined to find association with L-type CCBs. To identify the pathway of endocytosis, we tested with inhibitors of macropinocytosis, clathrin, and caveolae-mediated endocytosis.…”

Role of the DSC1 Channel in Regulating Neuronal Excitability in Drosophila melanogaster: Extending Nervous System Stability under Stress

“…The DSC1 channel could take part in the regulation of synaptic vesicle cycling, which is critical for synaptic transmission [24]. Both exocytotic release and re-uptake by endocytosis are controlled by Ca 2+ influx [24], [25]. Interestingly, the identity of the calcium channel that controls endocytosis at the presynaptic terminals has not been identified in insects, raising the intriguing possibility that the DSC1/BSC1 channel could be a candidate.…”