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Effects of endothelin-1 on K(+) currents from rat ventricular myocytes.
Biochem Biophys Res Commun. 2001 Jun 22; 284(4):1048-55.BB

Abstract

It has been suggested that the positive inotropic effect of the vasoactive peptide hormone, endothelin-1 (ET-1), involves inhibition of cardiac K(+) currents. In order to identify the K(+) currents modulated by ET-1, the outward K(+) currents of isolated rat ventricular myocytes were investigated using whole-cell patch-clamp recording techniques. Outward currents were elicited by depolarisation to +40 mV for 200 ms from the holding potential of -60 mV. Currents activated rapidly, reaching a peak (I(pk)) of 1310 +/- 115 pA and subsequently inactivating to an outward current level of 1063 +/- 122 pA at the end of the voltage-pulse (I(late)) (n = 11). ET-1 (20 nM) reduced I(pk) by 247.6 +/- 60.7 pA (n = 11, P < 0.01) and reduced I(late) by 323.2 +/- 43.9 pA (P < 0.001). The effects of ET-1 were abolished in the presence of the nonselective ET receptor antagonist, PD 142893 (10 microM, n = 5). Outward currents were considerably reduced and the effects of ET-1 were not observed when K(+) was replaced with Cs(+) in the experimental solutions; this indicates that ET-1 modulated K(+)-selective currents. A double-pulse protocol was used to investigate the inactivation of the currents. The voltage-dependent inactivation of the currents from potentials positive to -80 mV was fitted by a Boltzmann equation revealing the existence of an inactivating transient outward component (I(to)) and a noninactivating steady-state component (I(ss)). ET-1 markedly inhibited I(ss) by 43.0 +/- 3.8% (P < 0.001, n = 7) and shifted the voltage-dependent inactivation of I(to) by +3.3 +/- 1.2 mV (P < 0.05). Although ET-1 had little effect on the onset of inactivation of the currents elicited from a conditioning potential of -70 mV, the time-independent noninactivating component of the currents was markedly inhibited. In conclusion, the predominant effect of ET-1 was to inhibit a noninactivating steady-state background K(+) current (I(ss)). These results are consistent with the hypothesis that I(ss) inhibition contributes to the inotropic effects of ET-1.

Authors+Show Affiliations

Cardiac Physiology, Centre for Cardiovascular Biology and Medicine, The Rayne Institute, St. Thomas' Hospital, Lambeth Palace Road, London, SE1 7EH, United Kingdom. a.james@bristol.ac.ukNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11409900

Citation

James, A F., et al. "Effects of Endothelin-1 On K(+) Currents From Rat Ventricular Myocytes." Biochemical and Biophysical Research Communications, vol. 284, no. 4, 2001, pp. 1048-55.
James AF, Ramsey JE, Reynolds AM, et al. Effects of endothelin-1 on K(+) currents from rat ventricular myocytes. Biochem Biophys Res Commun. 2001;284(4):1048-55.
James, A. F., Ramsey, J. E., Reynolds, A. M., Hendry, B. M., & Shattock, M. J. (2001). Effects of endothelin-1 on K(+) currents from rat ventricular myocytes. Biochemical and Biophysical Research Communications, 284(4), 1048-55.
James AF, et al. Effects of Endothelin-1 On K(+) Currents From Rat Ventricular Myocytes. Biochem Biophys Res Commun. 2001 Jun 22;284(4):1048-55. PubMed PMID: 11409900.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of endothelin-1 on K(+) currents from rat ventricular myocytes. AU - James,A F, AU - Ramsey,J E, AU - Reynolds,A M, AU - Hendry,B M, AU - Shattock,M J, PY - 2001/6/21/pubmed PY - 2001/7/28/medline PY - 2001/6/21/entrez SP - 1048 EP - 55 JF - Biochemical and biophysical research communications JO - Biochem Biophys Res Commun VL - 284 IS - 4 N2 - It has been suggested that the positive inotropic effect of the vasoactive peptide hormone, endothelin-1 (ET-1), involves inhibition of cardiac K(+) currents. In order to identify the K(+) currents modulated by ET-1, the outward K(+) currents of isolated rat ventricular myocytes were investigated using whole-cell patch-clamp recording techniques. Outward currents were elicited by depolarisation to +40 mV for 200 ms from the holding potential of -60 mV. Currents activated rapidly, reaching a peak (I(pk)) of 1310 +/- 115 pA and subsequently inactivating to an outward current level of 1063 +/- 122 pA at the end of the voltage-pulse (I(late)) (n = 11). ET-1 (20 nM) reduced I(pk) by 247.6 +/- 60.7 pA (n = 11, P < 0.01) and reduced I(late) by 323.2 +/- 43.9 pA (P < 0.001). The effects of ET-1 were abolished in the presence of the nonselective ET receptor antagonist, PD 142893 (10 microM, n = 5). Outward currents were considerably reduced and the effects of ET-1 were not observed when K(+) was replaced with Cs(+) in the experimental solutions; this indicates that ET-1 modulated K(+)-selective currents. A double-pulse protocol was used to investigate the inactivation of the currents. The voltage-dependent inactivation of the currents from potentials positive to -80 mV was fitted by a Boltzmann equation revealing the existence of an inactivating transient outward component (I(to)) and a noninactivating steady-state component (I(ss)). ET-1 markedly inhibited I(ss) by 43.0 +/- 3.8% (P < 0.001, n = 7) and shifted the voltage-dependent inactivation of I(to) by +3.3 +/- 1.2 mV (P < 0.05). Although ET-1 had little effect on the onset of inactivation of the currents elicited from a conditioning potential of -70 mV, the time-independent noninactivating component of the currents was markedly inhibited. In conclusion, the predominant effect of ET-1 was to inhibit a noninactivating steady-state background K(+) current (I(ss)). These results are consistent with the hypothesis that I(ss) inhibition contributes to the inotropic effects of ET-1. SN - 0006-291X UR - https://www.unboundmedicine.com/medline/citation/11409900/Effects_of_endothelin_1_on_K_+__currents_from_rat_ventricular_myocytes_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(01)95083-1 DB - PRIME DP - Unbound Medicine ER -