Tags

Type your tag names separated by a space and hit enter

Inhibition of K+ channels by chlorpromazine in rat ventricular myocytes.
J Pharmacol Exp Ther. 1994 Nov; 271(2):632-7.JP

Abstract

Isolated rat ventricular myocytes were investigated with the whole-cell patch-clamp technique. Chlorpromazine inhibited inward-rectifying K+ currents (IC50 = 6.1 microM), time-independent outward currents (IC50 = 16 microM) and transient outward K+ currents. In the latter case, 100 microM of chlorpromazine reduced the amplitude of the peak current recorded at a clamp potential of 50 mV from 2.14 +/- 0.59 nA to 1.38 +/- 0.20 nA (n = 4) and decreased the time course of fast inactivation from 8.29 +/- 1.17 msec to 4.01 +/- 0.90 msec (n = 4). In addition, chlorpromazine blocked the ATP-dependent K+ current, which was activated either by the channel opener rilmakalim (10 microM) or by metabolic inhibition with carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP, 500 nM; IC50 for rilmakalim = 2.5 microM; IC50 for FCCP = 11.5 microM). The drug caused marked depolarization of the resting potential at higher concentrations (50 microM) from -79 +/- 3 mV to -27 +/- 11 mV (n = 4). The reversibility from channel block was slow and only partial for time-independent currents, especially inward-rectifying K+ currents, but it was relatively fast and complete for time-independent currents. Thus chlorpromazine blocks a variety of K+ channels in heart muscle cells. Inasmuch as the potency of inhibition is less than the previously reported use-dependent block of Na+ channels, the cardiovascular adverse effects of chlorpromazine are probably caused mainly by the latter effect.

Authors+Show Affiliations

Max-Planck-Institut für Biophysik, Frankfurt/Main, F.R.G.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

7965778

Citation

Kon, K, et al. "Inhibition of K+ Channels By Chlorpromazine in Rat Ventricular Myocytes." The Journal of Pharmacology and Experimental Therapeutics, vol. 271, no. 2, 1994, pp. 632-7.
Kon K, Krause E, Gögelein H. Inhibition of K+ channels by chlorpromazine in rat ventricular myocytes. J Pharmacol Exp Ther. 1994;271(2):632-7.
Kon, K., Krause, E., & Gögelein, H. (1994). Inhibition of K+ channels by chlorpromazine in rat ventricular myocytes. The Journal of Pharmacology and Experimental Therapeutics, 271(2), 632-7.
Kon K, Krause E, Gögelein H. Inhibition of K+ Channels By Chlorpromazine in Rat Ventricular Myocytes. J Pharmacol Exp Ther. 1994;271(2):632-7. PubMed PMID: 7965778.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of K+ channels by chlorpromazine in rat ventricular myocytes. AU - Kon,K, AU - Krause,E, AU - Gögelein,H, PY - 1994/11/1/pubmed PY - 1994/11/1/medline PY - 1994/11/1/entrez SP - 632 EP - 7 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 271 IS - 2 N2 - Isolated rat ventricular myocytes were investigated with the whole-cell patch-clamp technique. Chlorpromazine inhibited inward-rectifying K+ currents (IC50 = 6.1 microM), time-independent outward currents (IC50 = 16 microM) and transient outward K+ currents. In the latter case, 100 microM of chlorpromazine reduced the amplitude of the peak current recorded at a clamp potential of 50 mV from 2.14 +/- 0.59 nA to 1.38 +/- 0.20 nA (n = 4) and decreased the time course of fast inactivation from 8.29 +/- 1.17 msec to 4.01 +/- 0.90 msec (n = 4). In addition, chlorpromazine blocked the ATP-dependent K+ current, which was activated either by the channel opener rilmakalim (10 microM) or by metabolic inhibition with carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP, 500 nM; IC50 for rilmakalim = 2.5 microM; IC50 for FCCP = 11.5 microM). The drug caused marked depolarization of the resting potential at higher concentrations (50 microM) from -79 +/- 3 mV to -27 +/- 11 mV (n = 4). The reversibility from channel block was slow and only partial for time-independent currents, especially inward-rectifying K+ currents, but it was relatively fast and complete for time-independent currents. Thus chlorpromazine blocks a variety of K+ channels in heart muscle cells. Inasmuch as the potency of inhibition is less than the previously reported use-dependent block of Na+ channels, the cardiovascular adverse effects of chlorpromazine are probably caused mainly by the latter effect. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/7965778/Inhibition_of_K+_channels_by_chlorpromazine_in_rat_ventricular_myocytes_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=7965778 DB - PRIME DP - Unbound Medicine ER -