PubMed 15883157

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: ClvC2 , ClvC4 , Slo1

Title: Functional characterization of novel alternatively spliced ClC-2 chloride channel variants in the heart.

Authors: Fiona C Britton, Guan-Lei Wang, Z Maggie Huang, Linda Ye, Burton Horowitz, Joseph R Hume, Dayue Duan

Journal, date & volume: J. Biol. Chem., 2005 Jul 8 , 280, 25871-80

PubMed link:

A novel volume-regulated hyperpolarization-activated chloride inward rectifier channel ( was identified in mammalian heart. To investigate whether ClC-2 is the gene encoding channels in heart, ClC-2 cDNAs cloned from rat (rClC-2) and guinea pig (gpClC-2) hearts were functionally characterized. When expressed in NIH/3T3 cells, full-length rClC-2 yielded inwardly rectifying whole-cell currents with very slow activation kinetics (time constants > 1.7 s) upon hyperpolarization under hypotonic condition. The single-channel rClC-2 currents had a unitary slope conductance of 3.9 +/- 0.2 picosiemens. A novel variant with an in-frame deletion at the beginning of exon 15 that leads to a deletion of 45 bp (corresponding to 15 amino acids in alpha-helices O and P, rClC-2(Delta509-523)) was identified in rat heart. The relative transcriptional expression levels of full-length rClC-2 and rClC-2(Delta509-523) in rat heart were 0.018 +/- 0.003 and 0.028 +/- 0.006 arbitrary units, respectively, relative to glyceraldehyde-3-phosphate dehydrogenase (n = 5, p = nonsignificant). A similar partial exon 15 skipping with a deletion of 105 bp (35 amino acids in alpha-helices O-Q, gpClC-2(Delta509-543)) was also identified in guinea pig heart. Expression of both rClC-2(Delta509-523) and gpClC-2(Delta509-543) resulted in functional channels with phenotypic activation kinetics and many properties identical to those of endogenous channels in native rat and guinea pig cardiac myocytes, respectively. Intracellular dialysis of anti-ClC-2 antibody inhibited expressed ClC-2 channels and endogenous currents in native rat and guinea pig cardiac myocytes. These results demonstrate that novel deletion variants of ClC-2 due to partial exon 15 skipping may be expressed normally in heart and contribute to the formation of endogenous channels in native cardiac cells.