Two cDNAs encoding rabbit heart Cl− channels (rabClC-2β and rabClC-2α) were isolated by a PCR cloning strategy. RabClC-2β is a novel cDNA consisting of 2998 bp and encoding the 822-amino acid protein, while rabClC-2α is identical to previously reported ClC-2G. RabClC-2β is 68 amino acids truncated from NH2-terminus of rabClC-2α, but all 13 putative hydrophobic domains are conserved in rabClC-2β. Although rabClC-2α was suggested to be activated by extracellular hypotonicity, expression of rabClC-2β in Xenopus oocytes induced large Cl− currents even in the absence of extracellular hypotonicity. Induction of external hypotonicity did not further increase the amplitude of membrane currents. On the other hand, as similar to rabClC-2α, rabClC-2β current was augmented by PKA activation. Thus, different RNA processing of the same gene appears to provide two highly homologous PKA-activated Cl− channels with or without responsiveness to cell swelling in rabbit heart.
