Abstract
Whole-cell patch-clamp recording techniques were applied to measure INa in isolated ventricular myocytes of guinea pigs and CA1 neurons of hippocampus of Sprague-Dawley rats treated with L-thyroxine (0.5 mg/kg i.p. for 8-10 days). We found that the INa densities in both hypertrophied ventricular myocytes of guinea pigs and CA1 neurons of rats were reduced significantly. The peak current of -53.2±10.8 pA/pF (n=39) which was evoked at -30mV in the hypertrophied ventricular myocytes was significantly reduced when compared with -73.8±14.7 pA/pF in control myocytes (n=45, P<0.001). The maximal INa densities (at -60 mV membrane potential) of CA1 neurons in L-thyroxine-treated rats were reduced from 46.0±8.5 pA/pF to 38.9±8.3 pA/pF, respectively (n=20, P<0.05). After treatment with L-thyroxine, the decay of INa both in the ventricular myocytes of guinea pigs and CA1 neurons of rats was faster. The τ was 3.7±0.1 and 4.1±0.2 ms in the hypertrophied and control myocytes (P<0.05), respectively. The slow τ was accelerated from 3.87±1.28 in the control to 2.94±0.64 ms in the CA1 neurons of rats treated with L-thyroxine (P<0.05). No differences were found in the steady-state activation and inactivation and recovery kinetics in the hypertrophied ventricular myocytes. Our results indicate that impaired INa is involved in the heart and neurons in hyperthyroidism. A compromised INa for depolarization of the affected myocardium produces a slow conduction of cardiac impulses and provides a basis for uneven electrophysiological parameters. A reduced depolarizing INa combined with an impaired ion current for repolarization contribute to arrhythmogenesis of the remodeled ventricle.
Original language | English (US) |
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Pages (from-to) | 111-115 |
Number of pages | 5 |
Journal | Drug Development Research |
Volume | 58 |
Issue number | 1 |
DOIs | |
State | Published - Jan 1 2003 |
Externally published | Yes |
All Science Journal Classification (ASJC) codes
- Drug Discovery
Keywords
- L-thyroxine
- Sodium currents
- Ventricular hypertrophy