Effects of chloride ion substitutes and chloride channel blockers on the transient outward current in rat ventricular myocytes

13Citations
Citations of this article
5Readers
Mendeley users who have this article in their library.

Abstract

The Ca(i)2+-insensitive transient outward current, i(lo), was studied at 20-24°C in rat ventricular myocytes with the whole cell recording patch-clamp technique. The current was recorded before and after replacement of chloride by methanesulfonate or aspartate or in the absence and the presence of chloride channel blockers, SITS or 9-anthracene carboxylic acid. In control conditions (in the presence of external divalent cations, Ca2+ and Cd2+, Cd2+ being used to suppress Ca2+current), i(lo) inactivation was composed of a fast and a slow component. When methanesulfonate was substituted for external Cl-, the peak current decreased to a variable extent, but the inactivation of the remaining current was still composed of a fast and a slow component. In contrast, the inactivation of the difference current was well fitted by a single exponential. The time to peak of the difference current was shorter than that of the current recorded either in the absence or the presence of methanesulfonate. Both activation- and steady-state inactivation-voltage curves were either unchanged (n = 4) or shifted by a few mV (5.5 mV, n = 14) towards positive potentials when methanesulfonate was substituted for Cl-. The current remaining in methanesulfonate reversed at potentials closed to E(K). The difference current was composed of a peak and a steady-state component. The peak was suppressed by 4-aminopyridine whereas the steady-state component was not. The peak was also suppressed when pipette solution contained Cs+ instead of K+ but was still present when the Hepes concentration in both external and pipette media was increased S-fold (50 mM vs. 10 mM). When aspartate was substituted for Cl- or when 2 mM SITS was added to the external solution (in the absence of Ca2+ and Cd2+ because aspartate is known to chelate Ca2+ ions and possibly other divalent cations), i(lo) was reduced to a similar extent in the two cases and the difference current was composed of a peak (inactivation fitted by a single exponential) and a steady-state component. The SITS-sensitive transient current reversed at a potential close to E(Cl). When 5 mM 9-anthracene carboxylic acid was added to external solution (in the presence of Ca2+ and Cd2+), the peak of the difference current was similar to that observed when Cl- was substituted by methanesulfonate. The difference current resulting from the substitution of methanesulfonate for chloride was not changed when the pipette solution contained either 50 mM EGTA (instead of 5 mM) or 10 mM EGTA and 10 mM BAPTA. The nature of Cs+- and 4-aminopyridine-sensitive transient outward current suppressed by chloride ion substitutes or chloride channel blockers is discussed.

Cite

CITATION STYLE

APA

Lefevre, T., Lefevre, I. A., Coulombe, A., & Coraboeuf, E. (1996). Effects of chloride ion substitutes and chloride channel blockers on the transient outward current in rat ventricular myocytes. Biochimica et Biophysica Acta - Bioenergetics, 1273(1), 31–43. https://doi.org/10.1016/0005-2728(95)00127-1

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free