@article {Castiglioni:2006:0022-3751:119,
author = "Castiglioni, Andrew J. and Raingo, Jesica and Lipscombe, Diane",
title = "Alternative splicing in the C-terminus of CaV2.2 controls expression and gating of N-type calcium channels",
journal = "The Journal of Physiology",
volume = "576",
number = "1",
year = "2006",
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.",
pages = "119-134",
url = "http://www.ingentaconnect.com/content/bsc/tjp/2006/00000576/00000001/art00015",
doi = "doi:10.1113/jphysiol.2006.115030"
}