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Metabolic inhibition of ICa,L and IK differs in feline left ventricular hypertrophy
T Furukawa1, R J Myerburg, N Furukawa
1Department of Medicine, University of Miami School of Medicine, Florida 33101-6189.
Insights
Hypertrophied heart cells show greater changes in electrical activity during metabolic stress. This intrinsic responsiveness is linked to alterations in calcium (Ca2+) currents in hypertrophied cells.
Area of Science:
- Cardiovascular Physiology
- Cardiac Electrophysiology
- Myocardial Hypertrophy
Background:
- Cardiac hypertrophy, a thickening of the heart muscle, can alter cellular electrophysiology.
- Understanding the intrinsic electrical properties of hypertrophied myocytes is crucial for assessing cardiac function under stress.
Purpose of the Study:
- To investigate the intrinsic electrophysiological responsiveness of hypertrophied feline left ventricular (LV) myocytes during metabolic inhibition.
- To compare the effects of cyanide (CN-) on action potentials and membrane currents in normal versus hypertrophied LV myocytes.
Main Methods:
- Enzymatic dissociation of endocardial myocytes from normal and hypertrophied feline left ventricles.
- Whole-cell patch-clamp technique to record action potentials and membrane currents.
- Metabolic inhibition induced by 1 mM cyanide (CN-) exposure.
Main Results:
- Hypertrophied myocytes exhibited longer action potential durations (APD) and altered L-type Ca2+ currents (ICa,L) and delayed rectifier K+ currents (IK) prior to CN- exposure.
- During CN- exposure, hypertrophied cells showed a greater APD shortening and significant changes in ICa,L inactivation kinetics.
- IK current kinetics and amplitude remained largely similar between normal and hypertrophied cells during metabolic inhibition.
Conclusions:
- Enhanced APD responsiveness to metabolic inhibition is an intrinsic property of hypertrophied LV myocytes.
- L-type Ca2+ currents (ICa,L) are particularly susceptible to metabolic perturbation in hypertrophied cardiac cells.
Abstract:
To determine the intrinsic responsiveness of hypertrophied myocardium, electrophysiological properties of endocardial myocytes enzymatically dissociated from normal and hypertrophied feline left ventricle (LV) were compared during metabolic inhibition by 1 mM CN-. Chronic pressure overload was induced under surgical anesthesia. A single-pipette, whole cell clamp method was used to record action potential and membrane currents. Before CN-, action potential duration (APD) values at 90% repolarization (APD90) and at 0 mV (APD0mV) were significantly longer in hypertrophied cells. The current density of L-type Ca2+ currents (ICa,L) was not significantly different, whereas the time constant of the slow component (tau s) of ICa,L inactivation was significantly longer in hypertrophied cells. The current density of delayed rectifier K+ current (IK) was significantly smaller, the fast component (tau f) and tau s of IK activation were delayed, and those of IK deactivation were enhanced in hypertrophied cells. During exposure to CN-, APD shortened significantly more in hypertrophied cells; amplitude of ICa,L decreased, and the tau f and tau s of ICa,L inactivation shortened only in hypertrophied cells. However, IK showed no significant differences in changes in amplitude or kinetics during CN- exposure between normal and hypertrophied cells. Thus enhanced APD responsiveness to CN- is an intrinsic property of hypertrophied LV cells and ICa,L appears to be particularly affected by metabolic perturbation in such cells.