Key result
Blockade of the Ca2+-activated Cl- current by DIDS increased action potential duration in subendocardial myocytes at all frequencies, but only at high frequencies in subepicardial myocytes.
Why the study?
Does blockade of ICl(Ca) alter action potential duration in rabbit ventricular myocytes?
Does blockade of ICl(Ca) alter action potential duration in rabbit ventricular myocytes?
The Ca2+-activated Cl- current contributes to action potential duration shortening in subendocardial myocytes, reducing electrical heterogeneity in the rabbit left ventricle.
Animal data link ICl(Ca) to regional APD control in rabbit ventricle; leaves open relevance to human transmural heterogeneity.
OBJECTIVE: Various cationic membrane channels contribute to the heterogeneity of action potential configuration between the transmural layers of the left ventricle. The role of anionic membrane channels is less intensively studied. We investigated the role of the Ca2+-activated Cl- current, ICl(Ca), in transmural electrical heterogeneity. METHODS AND RESULTS: We determined the density of ICl(Ca) and its physiological role in subepicardial and subendocardial ventricular myocytes of rabbit using the patch-clamp technique. ICl(Ca) was measured as the 4,4'diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS) sensitive current. The current-voltage relationships and the densities of ICl(Ca) were similar in subepicardial and subendocardial myocytes. However, the functional role of ICl(Ca) exhibited striking differences. In subendocardial myocytes, blockade of ICl(Ca) by DIDS increased action potential duration (APD) significantly at all measured stimulus frequencies (3.33-0.2 Hz). In subepicardial myocytes, ICl(Ca) blockade increased APD only at 3.33 Hz, but not at the lower stimulus frequencies. At 1 Hz, ICl(Ca) blockade in subepicardial myocytes only caused an APD increase when the transient outward K+ current, Ito1, was blocked. CONCLUSIONS: The densities and gating properties of ICl(Ca) are similar in subepicardial and subendocardial myocytes. ICl(Ca) contributes to APD shortening in subendocardial, but not in subepicardial myocytes except at 3.33 Hz. These differences in functional expression of ICl(Ca) reduce the electrical heterogeneity in rabbit left ventricle.
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Verkerk et al. (2004) studied Normal rabbit ventricular myocytes. Blockade of ICl(Ca) by DIDS vs. Unblocked state was evaluated on Action potential duration (APD). Blockade of the Ca2+-activated Cl- current by DIDS increased action potential duration in subendocardial myocytes at all frequencies, but only at high frequencies in subepicardial myocytes.
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