Basal late sodium current is a significant contributor to the duration of action potential of guinea pig ventricular myocytes

In cardiac myocytes, an enhancement of late sodium current (I(N) (aL)) under pathological conditions is known to cause prolongation of action potential duration (APD). This study investigated the contribution of I(N) (aL) under basal, physiological conditions to the APD. Whole‐cell I(N) (aL) and the APD of ventricular myocytes isolated from healthy adult guinea pigs were measured at 36°C. The I(N) (aL) inhibitor GS967 or TTX was applied to block I(N) (aL). The amplitude of basal I(N) (aL) and the APD at 50% repolarization in myocytes stimulated at a frequency of 0.17 Hz were ‐0.24 ± 0.02 pA/pF and 229 ± 6 msec, respectively. GS967 (0.01–1 μmol/L) concentration dependently reduced the basal I (NaL) by 18 ± 3–82 ± 4%. At the same concentrations, GS967 shortened the APD by 9 ± 2 to 25 ± 1%. Similarly, TTX at 0.1–10 μmol/L decreased the basal I (NaL) by 13 ± 1–94 ± 1% and APD by 8 ± 1–31 ± 2%. There was a close correlation (R (2) = 0.958) between the percentage inhibition of I(N) (aL) and the percentage shortening of APD caused by either GS967 or TTX. MTSEA (methanethiosulfonate ethylammonium, 2 mmol/L), a Na(V)1.5 channel blocker, reduced the I (NaL) by 90 ± 5%, suggesting that the Na(V)1.5 channel isoform is the major contributor to the basal I (NaL). KN‐93 (10 μmol/L) and AIP (2 μmol/L), blockers of CaMKII, moderately reduced the basal I (NaL). Thus, this study provides strong evidence that basal endogenous I (NaL) is a significant contributor to the APD of cardiac myocytes. In addition, the basal I (NaL) of guinea pig ventricular myocytes is mainly generated from Na(V)1.5 channel isoform and is regulated by CaMKII.