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Basal late sodium current is a significant contributor to the duration of action potential of guinea pig ventricular myocytes
Author(s) -
Song Yejia,
Belardinelli Luiz
Publication year - 2017
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.13295
Subject(s) - basal (medicine) , guinea pig , myocyte , medicine , sodium , duration (music) , cardiology , endocrinology , biology , chemistry , physics , organic chemistry , insulin , acoustics
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 GS 967 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. GS 967 (0.01–1  μ mol/L) concentration dependently reduced the basal I NaL by 18 ± 3–82 ± 4%. At the same concentrations, GS 967 shortened the APD by 9 ± 2 to 25 ± 1%. Similarly, TTX at 0.1–10  μ mol/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 GS 967 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  μ mol/L) and AIP (2  μ mol/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.

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