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Four different components contribute to outward current in rat ventricular myocytes
1Institut für Pharmakologie, Universität Gesamthochschule Essen, D-45122 Essen, Germany. himmel@rcs.urz.tu-dresden.de
The American Journal of Physiology
|July 17, 1999
Summary
Researchers identified four distinct outward potassium (K+) current components in rat ventricular myocytes using electrophysiological and pharmacological methods. This expands our understanding of cardiac electrical activity and K+ channel diversity.
Area of Science:
- Cardiac Electrophysiology
- Ion Channel Physiology
- Molecular Cardiology
Background:
- Rat ventricle myocytes possess known 4-aminopyridine (4-AP)-sensitive transient outward K+ current (I(to)) and tetraethylammonium (TEA)-sensitive sustained K+ current (I(K)).
- Discrepancies exist between identified K+ currents and the diversity of K+ channel mRNA and protein expression.
- Further electrophysiological investigation is needed to identify additional K+ current components.
Purpose of the Study:
- To identify and characterize distinct electrophysiological components of outward K+ currents in rat ventricular myocytes.
- To investigate the kinetic and pharmacological properties of these current components.
Main Methods:
- Whole-cell voltage-clamp technique was employed to analyze steady-state inactivation of outward currents.
- Conditioning potentials were applied over a wide voltage range.
- Peak (I(peak)) and late (I(late)) currents were analyzed using Boltzmann curve fitting to determine inactivation properties and identify current fractions.
Main Results:
- Analysis revealed three inactivating fractions (a, b) and one non-inactivating fraction (r) for both I(peak) and I(late).
- Fraction b of I(peak) was transient, consistent with I(to). Fractions a, b, and r of I(late) represented sustained currents.
- Four distinct outward current components were identified: I(to) (transient), I(K) (sustained, fraction a), steady-state current I(ss) (non-inactivating, fraction r), and a novel sustained current I(Kx) (sustained, fraction b of I(late)).
- These currents showed differential sensitivity to various K+ channel blockers (TEA, 4-AP, clofilium, quinidine, dendrotoxin, heteropodatoxin, hanatoxin).
Conclusions:
- At least four distinct outward K+ current components (I(to), I(K), I(ss), I(Kx)) contribute to action potential generation in rat ventricular myocytes.
- These currents exhibit unique kinetic and pharmacological profiles, supporting their distinct identities.
- The findings reconcile electrophysiological data with the known diversity of K+ channels in the heart.