Nonselective cation current in rabbit ventricular myocytes

• Published in: Methods and findings in experimental and clinical pharmacology Vol. 27; no. 6; pp. 377 - 383
• Main Authors: SONG, Y.-D, YANG, X.-C, LIU, T.-F, GU, Z.-W
• Format: Journal Article
• Language: English
• Published: Barcelona Prous 01-07-2005
• Subjects: 4-Aminopyridine - pharmacology; Action Potentials - drug effects; Animals; Barium Compounds - pharmacology; Biological and medical sciences; Cadmium Chloride - pharmacology; Calcium - pharmacology; Calcium Channel Blockers - pharmacology; Cesium - pharmacology; Chlorides - pharmacology; Gadolinium - pharmacology; General pharmacology; Heart Ventricles - drug effects; In Vitro Techniques; Insulin; Ion Channels - drug effects; Ion Channels - physiology; Magnesium - pharmacology; Medical sciences; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - physiology; Patch-Clamp Techniques; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Potassium - pharmacology; Potassium Channel Blockers - pharmacology; Rabbits; Sodium - pharmacology; Ventricular Function; Pancreatic hormone; Ca2+ and Mg2; Pharmaceutical technology; Calcium; Rabbit; Gadolinium; Lagomorpha; Inorganic element; Insulin; Myocyte; Vertebrata; Mammalia; Animal; Nonselective cation current; Cations; Rabbit ventricular myocytes
• ISSN: 0379-0355
• DOI: 10.1358/mf.2005.27.6.916676

Currents contributing repolarization in rabbit ventricular myocytes are very complex because the I(to.s) covers almost the whole repolarization phase of the action potential. The other components of repolarizing currents, such as I(Kr) and I(Ks), are small. In the present work, with whole-cell patch-clamp technique, a clear evidence was provided for the existence of a hitherto unreported, voltage-dependent, nonselective cation current (NSCC) in rabbit ventricular myocytes. Na(+), K(+), and Cs(+) can permeate through the nonselective cation channel and the NSCC can be blocked by Gd(3+). The channels are sensitive to Ca(2+), Mg(2+)-free, and insulin in bathing solution. Activation of NSCC may provide complex effects on action potential configuration depending on the basal conditions and the experimental situations. Considering the voltage dependence and rapid activation kinetics of this current, we speculate that this current can provide an important influence on all repolarization phases of the action potential as well as contribute to the resting membrane potential in rabbit ventricular myocytes. In addition, it is conceivable that, under certain pathophysiological conditions (e.g., ischemia or excessive mechanical stress), the sensitivity of the channels could be altered in such a way that the conductance opens even in the presence of physiological Ca(2+), Mg(2+), and insulin. It might be an important factor on the repolarization of the action potential. Changes in NSCC may lead to an induction or inhibition of arrhythmia.