Ca2+-activated Cl- current reduces transmural electrical heterogeneity within the rabbit left ventricle

Area of Science:

• Cardiovascular Physiology
• Electrophysiology
• Ion Channel Function

Background:

• Cationic channels influence cardiac action potential heterogeneity.
• Anionic channels, particularly ICl(Ca), are less understood in this context.
• Investigating ICl(Ca) is crucial for understanding transmural electrical differences.

Purpose of the Study:

• To investigate the role of Ca2+-activated Cl- current (ICl(Ca)) in left ventricular transmural electrical heterogeneity.
• To compare the density and functional significance of ICl(Ca) in subepicardial and subendocardial myocytes.

Main Methods:

• Patch-clamp technique on rabbit ventricular myocytes.
• Measurement of ICl(Ca) as the 4,4'diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS) sensitive current.
• Assessment of ICl(Ca) role in action potential duration (APD) at various stimulus frequencies.

Main Results:

• ICl(Ca) density and current-voltage relationships were similar in both myocyte types.
• ICl(Ca) blockade significantly prolonged APD in subendocardial myocytes across frequencies.
• In subepicardial myocytes, ICl(Ca) blockade prolonged APD only at high frequencies or when Ito1 was also blocked.

Conclusions:

• ICl(Ca) densities and gating are uniform across rabbit ventricular transmural layers.
• ICl(Ca) functionally contributes to APD shortening in subendocardial, but not subepicardial, myocytes.
• Differential functional expression of ICl(Ca) mitigates transmural electrical heterogeneity in the rabbit left ventricle.