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Effects of pressure overload-induced hypertrophy on TTX-sensitive inward currents in guinea pig left ventricle

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Abstract

We investigated the effects of pressure overload hypertrophy on inward sodium (I Na) and calcium currents (I Ca) in single left ventricular myocytes to determine whether changes in these current systems could account for the observed prolongation of the action potential. Hypertrophy was induced by pressure overload caused by banding of the abdominal aorta. Whole-cell patch clamp experiments were used to measure tetrodotoxin (TTX)-sensitive inward currents. The main findings were that I Ca density was unchanged whereas I Na density after stepping from −80 to −30 mV was decreased by 30% (−9.0 ± 1.16 pA pF−1 in control and −6.31 ± 0.67 pA pF−1 in hypertrophy, p < 0.05, n= 6). Steady-state activation/inactivation variables of I Na, determined by using double-pulse protocols, were similar in control and hypertrophied myocytes, whereas the time course of fast inactivation of I Na was slowed (p < 0.05) in hypertrophied myocytes. In addition, action potential clamp experiments were carried out in the absence and presence of TTX under conditions where only Ca2+ was likely to enter the cell via TTX-sensitive channels. We show for the first time that a TTX-sensitive inward current was present during the plateau phase of the action potential in hypertrophied but not control myocytes. The observed decrease in I Na density is likely to abbreviate rather than prolong the action potential. Delayed fast inactivation of Na+ channels was not sustained throughout the voltage pulse and may therefore merely counteract the effect of decreased I Na density so that net Na+ influx remains unaltered. Changes in the fast I Na do not therefore appear to contribute to lengthening of the action potential in this model of hypertrophy. However, the presence of a TTX-sensitive current during the plateau could potentially contribute to the prolongation of the action potential in hypertrophied cardiac muscle. (Mol Cell Biochem 261: 217–226, 2004)

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  1. Department of Medicine, University Clinical Departments, Duncan Building, Daulby Street, Liverpool, L69 3GA, UK

    Alzbeta Chorvatova, Richard Snowdon, George Hart & Munir Hussain

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  1. Alzbeta Chorvatova
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  2. Richard Snowdon
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  3. George Hart
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  4. Munir Hussain
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Chorvatova, A., Snowdon, R., Hart, G. et al. Effects of pressure overload-induced hypertrophy on TTX-sensitive inward currents in guinea pig left ventricle. Mol Cell Biochem 261, 217–226 (2004). https://doi.org/10.1023/B:MCBI.0000028759.22274.cf

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