Divalent cation channels activated by phenothiazines in membrane of rat ventricular myocytes |
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Authors: | T Lefevre E Coraboeuf A Ghazi A Coulombe |
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Institution: | (1) Laboratoire de Cardiologie Moléculaire et Cellulaire (CNRS URA 1159), Hôpital Marie Lannelongue, F-92350 Le Plessis Robinson, France;(2) Laboratoire de Physiologie Cellulaire, (CNRS URA 1121), Université Paris-Sud, Bâtiment 443, F-91405 Orsay Cedex, France;(3) Laboratoire des Biomembranes (CNRS URA 1119), Université Paris-Sud, Bâtiment 443, F-91405 Orsay Cedex, France |
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Abstract: | Phenothiazines (PTZ) such as chlorpromazine (CPZ) or trifluoperazine (TPZ) induced a sustained divalent cation-permeable channel activity when applied on either side of inside-out patches or on external side of cell-attached patches of adult rat ventricular myocytes. The percentage of active patches was 20%. In the case of CPZ, the K
dof the dose-response curve was 160 m. CPZ-activated channels were potential-independent in the physiological range of membrane potential and were permeable to several divalent ions (Ba2+, Ca2+, Mg2+, Mn2+). At least three levels of currents were usually detected with conductances of 23, 50 and 80 pS in symmetrical 96 mm Ba2+ solution and 17, 36 and 61 pS in symmetrical 96 mm Ca2+ solution. Saturation curves corresponding to the three main conductances determined in Ba2+ symmetrical solutions (tonicity compensated with choline-Cl) gave maximum conductances of 36, 81 and 116 pS (with corresponding half-saturating concentration constants of 31.5, 38 and 34.5 mm). The corresponding conductance values were estimated to 1.7, 3.3 and 5.2 pS in symmetrical 1.8 mm Ba2+ and to 1.1, 2.4 and 3.7 pS in symmetrical 1.8 mm Ca2+ (the value in normal Tyrode solution). Channels were poorly permeable to monovalent cations, such as Na, with a P
Ba/P
Na ratio of 10. A PTZ-induced channel activity similar to that described in cardiac cells was also observed in cultured rat aortic smooth muscle cells but not in cultured neuroblastoma cells.PTZ-activated channels described in cardiac cells appear very similar to the sporadically active divalent ion permeable channels described in a previous paper (Coulombe et al., 1989). Surprisingly, when 100 m CPZ were applied to myocytes studied in the whole-cell configuration, and maintained at a holding potential of –80 mV in the presence of 24 mm external Ca2+ or Ba2+, no detectable macroscopic inward current could be observed, whereas the L-type Ca2+ current triggered by depolarizing pulses was markedly and reversibly reduced. The possible reasons are discussed. |
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Keywords: | Rat ventricular myocytes Calcium background channels Chlorpromazine Trifluoperazine W-7 Polymixin B |
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