Anoctamin‐1 channel localization in excitable domains of the heart (893.23)

Abstract

Calcium‐activated chloride (ClCa) currents are widely distributed in cardiac tissues and have been implicated to play a role in cardiac physiology and pathophysiology. Anoctamin‐1 (Ano1) is a membrane protein that functions as a ClCa channel and has been linked to essential physiological roles in a variety of excitable cells. We hypothesized that Ano1 channels in their functional role as ClCa channels are localized in distinct regions of the heart. Our objective was to define the localization and cellular expression of Ano1 channels in heart. Confocal immunofluorescence microscopy of mouse heart indicated that Ano1 channels are clustered at the intercalated discs of cardiac myocytes. We demonstrated strong co‐localization of Ano1 with connexin‐43 (Cx43) gap junction protein in isolated ventricular and atrial myocytes. A direct interaction between Ano1 channels and Cx43 was verified by co‐immunoprecipitation using mouse heart lysates. Our findings reveal that Ano1 channels compartmentalize in the intercalated disc region and suggest that Ano1 channels may play an important role in cell‐cell communication in this excitable membrane domain.Grant Funding Source: Supported by RO1HL091238