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Restoration of action potential duration and transient outward current by regression of left ventricular hypertrophy
H Yokoshiki1, T Kohya, F Tomita
1Department of Cardiovascular Medicine, Hokkaido University School of Medicine, Japan.
Insights
Regression of left ventricular hypertrophy (LVH) normalizes action potential duration and reduces lethal arrhythmias. This study shows restoring transient outward current (ito) density in regressed LVH cells prevents arrhythmias.
Area of Science:
- Cardiology
- Electrophysiology
- Pharmacology
Background:
- Left ventricular hypertrophy (LVH) is linked to increased arrhythmia incidence.
- LVH regression in rat hearts prevents lethal arrhythmias, but the mechanism is unclear.
Purpose of the Study:
- To investigate the electrophysiological mechanisms underlying reduced arrhythmias in regressed LVH.
- To compare action potentials and membrane currents in hypertrophied and regressed left ventricular cells.
Main Methods:
- Utilized spontaneously hypertensive rats (SHR) for LVH and Wistar-Kyoto rats (WKY) as controls.
- Induced LVH regression (REG) in SHR using captopril treatment.
- Employed whole-cell patch-clamp techniques to analyze electrophysiological properties of subendocardial left ventricular cells.
Main Results:
- SHR cells exhibited significantly greater membrane capacitance and prolonged action potential duration (APD) with reduced transient outward current (ito) density compared to WKY.
- LVH regression (REG) normalized membrane capacitance and APD, and restored ito density to control levels.
- No significant differences in other measured membrane currents (steady-state outward, inward rectifier, L-type Ca2+) were observed.
Conclusions:
- LVH regression normalizes prolonged APD in hypertrophied hearts by restoring ito density.
- This restoration of ito is a potential causal mechanism for the reduced incidence of arrhythmias observed in regressed LVH.
Abstract:
The presence of left ventricular hypertrophy (LVH) is associated with an increased incidence of arrhythmias. Our previous study on hypertrophied rat hearts has demonstrated that regression of LVH prevents ischemia-induced lethal arrhythmias. To elucidate the underlying mechanism of the reduced incidence of arrhythmias in regression of LVH, we examined electrophysiological properties of both hypertrophied and regressed left ventricular cells. Hearts from spontaneously hypertensive rats (SHR) were used as LVH, and those from Wistar-Kyoto rats (WKY) served as control. SHR with regression of LVH (REG) was produced by captopril treatment. Action potentials and membrane currents of subendocardial left ventricular cells were compared by the whole-cell patch-clamp techniques. Although the membrane capacitance of SHR cells was significantly greater than that of WKY cells, that of REG cells was normalized to the control level. Prolonged action potential duration (APD) and reduced density of transient outward current (ito) in SHR cells was normalized by LVH regression (APD at 75% repolarization (ms) and ito density at +60 mV (pA/pF): WKY 36.1 +/- 4.2, 11.9 +/- 1.3, SHR 73.1 +/- 12.9, 5.2 +/- 0.7, REG 29.5 +/- 3.9, 10.4 +/- 2.0, P = 0.015, P = 0.001 v WKY). No significant differences were observed in the densities of steady-state outward current, inward rectifier current, and L-type Ca2+ current. The restoration of ito density by regression of LVH could normalize the prolonged APD in hypertensive LVH, which may be causally related to the reduced incidence of arrhythmias in LVH regression.