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- Title
Alternative splicing in the C-terminus of Ca<sub>V</sub>2.2 controls expression and gating of N-type calcium channels.
- Authors
Castiglioni, Andrew J.; Raingo, Jesica; Lipscombe, Diane
- Abstract
N-type CaV2.2 calcium channels localize to presynaptic nerve terminals of nociceptors where they control neurotransmitter release. Nociceptive neurons express a unique set of ion channels and receptors important for optimizing their role in transmission of noxious stimuli. Included among these is a structurally and functionally distinct N-type calcium channel splice isoform, CaV2.2e[37a], expressed in a subset of nociceptors and with limited expression in other parts of the nervous system. CaV2.2[e37a] arises from the mutually exclusive replacement of e37a for e37b in the C-terminus of CaV2.2 mRNA. N-type current densities in nociceptors that express a combination of CaV2.2e[37a] and CaV2.2e[37b] mRNAs are significantly larger compared to cells that express only CaV2.2e[37b]. Here we show that e37a supports increased expression of functional N-type channels and an increase in channel open time as compared to CaV2.2 channels that contain e37b. To understand how e37a affects N-type currents we compared macroscopic and single-channel ionic currents as well as gating currents in tsA201 cells expressing CaV2.2e[37a] and CaV2.2e[37b]. When activated, CaV2.2e[37a] channels remain open for longer and are expressed at higher density than CaV2.2e[37b] channels. These unique features of the CaV2.2e[37a] isoform combine to augment substantially the amount of calcium that enters cells in response to action potentials. Our studies of the e37a/e37b splice site reveal a multifunctional domain in the C-terminus of CaV2.2 that regulates the overall activity of N-type calcium channels in nociceptors.
- Publication
Journal of Physiology, 2006, Vol 576, Issue 1, p119
- ISSN
0022-3751
- Publication type
Academic Journal
- DOI
10.1113/jphysiol.2006.115030