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Ischemia-induced modifications of the potassium currents. Effects of the potassium channel activator, cromakalim, in Purkinje fibers surviving infarction
J Mol
Cell
Cardiol21
(Supplement
IV)(1989)
PI33
ISCHBMIA-INDUCED MODIFICATIONS OF THE POTASSIUM CURRENTS. EFFECTS OF THE POTASSIUM CHANNEL ACTIVATOR, CROMAKALIM, IN PIJRKINJE FIBERS SURVIVING INFARCTION. A. Brill and R.Y.K. Man ; University of Manitoba ; Winnipeg, Man. ; Canada R3EOW3. The effects of various concentrations (l-100 pM) of Cromakalim (C) on the action potentials of canine Purkinje fibers surviving infarction (PFSI), were investigated. To clarify the role of the K' conductance in these fibers, the electrophysiological activity of C has been examined in normal Purkinje fibers (NPF) and in fibers in which the K' conductance has been reduced by barium (BaPF). In NPF, C produced concentration-dependent shortening in action potential duration without change in the membrane diastolic potential. in the action potential amplitude or in the maximum upstroke ve-locity. A similar shortening was observed in PFSI and in BaPF. The shortening effect of C was more pronounced at a longer stimulation cycle length than at a short cycle length. In NPF and in PFSI. depolarizations produced by low K' (<2mM) were reversed by C. whereas there were no effects on high K+ (4&M)-induced depolarization. However BaPF were not sensitive to the hyperpolarizing effect of C. It is proposed that the electrophysiological activity of C in canine Purkinje fibers is related to an increase in the K' currents, i, and i,, in these fibers. These results also suggest that the modifications seen in PFSI could be due to a decrease in i, and a partial reduction in i,l. (supported by Manitoba Heart Foundation, we thank Beecham UK for their supply of C). 1 present address : Les Laboratoires Beecham. Rennes, France.
P134
ELECTROPHYSIOLOGICAL EFFECTS OF THE HYPOGLYCEMIC SULPHONYLUREAS ON THE HEART. G. Pogitsa, J. G. Papp, M. 2. Koltai, Z. Aranyi, G. Ballagi-Porddny, M. Jakab. Research Department, National Institute of Cardiology, Budapest, Hungary. Previous studies have demonstrated a difference among effects of various hypoglycemic sulphonylureas on myocardial contractile force and arterial blood pressure. Various sulphonylurea drugs (1 mM - 1 PM) were compared, therefore, as to their influence on the electrical activity of isolated rabbit heart preparations as well as on the arrhythmogenity of strophantinized rabbit and infarcted rat hearts. In Purkinjc fibers only glibenclamide depressed automaticity and increased conduction velocity and electrical threshold. Carbutamide, tolbutamide gliclazide and glipizide enhanced or did not influenced automaticity and decreased conduction velocity and electrical threshold. None of drugs affected resting membrane potential. All investigated compounds depressed maximal velocity of membrane depolarization and phase of partial recovery of transmembrane potential. Not any of investigated sulphonylureas influenced electrical threshold and conduction velocity in the auricle. Glibenclamide and glipizide decreased, whereas carbutamide, tolbutamide and gliclazide enhanced incidence of ventricular ectopic beats both in strophanthin treated rabbit and in infarcted rat hearts. All effects were dose-dependent, and differed also when identical molar levels were used. It follows that glibenclamide differs from other hypoglycemic drugs with respect to its influences on cardiac electrical activity.
PI35
GEUilSIS OF EARLY A?TER'?EPOL%IZATII)N IN pOl]SE ATRlAL F1RI;R.i AND ,T;, 'NHIHIT;NG AGSNTS. T-F. Liu. Department Of B;olory, Peking IlniversIty! Re:jinp, China. Ea;-!y afterdepolarizations (CADS) can be easily induced in mouse rtr-ial fibers Undel 1.5 nti; K spaI~AFS) by reduction of the concentration of I< in the superfusate. percusion, the &ADS appeared on the baclr~rourd of automatic,ity of the AF, while under 3-n d.i K treatment, the action potential Lept normal with the cycle length of driving stimlllat;on less thar. 0.5 s. Prolongation of tte (,ycle length to 1 s or more The c 3,3,4 and 5 s), EHDC appeared gradually showing its cycle lf?ngth dependence. relationship between cycle length and numder and duratiun of tripeered bursts ware inear, at least in the rarge of 1 to 5 s cycle length. Application of an extra stimulation i)T: the early repolarizatjon phase C-40 to -60 mV level) of an action potenmore than one response could be induced, tial without Exi, under 3.0 tii K superfusion, was defined as 'se<,ond plateau pivirlg a similar corfiguration of 8:riD. This phenomenon E&S could be suppr-ssed by l"lX, lidoraint,, verapamil, nifedipine and Tl+ response'. leaIcing the linear relationship bet.weeri cycle IenLth and tt,e parameters resp&ctively, rjhen t.tle EI'.D% wore inhibited by tte above agents completfly, the of E/D unchanged. cap be regarded second plateau responses disappeared concurrently. So, t,\e latt,,r It is suggested that all the ionic currentrj contributing as an indicator uf the EaD. to the plateau phase formaticn arr responsible to the FeneSiS :of EAD. '.%e
s.54
Cell
Cardiol21
(Supplement
IV)(1989)
PI33
ISCHBMIA-INDUCED MODIFICATIONS OF THE POTASSIUM CURRENTS. EFFECTS OF THE POTASSIUM CHANNEL ACTIVATOR, CROMAKALIM, IN PIJRKINJE FIBERS SURVIVING INFARCTION. A. Brill and R.Y.K. Man ; University of Manitoba ; Winnipeg, Man. ; Canada R3EOW3. The effects of various concentrations (l-100 pM) of Cromakalim (C) on the action potentials of canine Purkinje fibers surviving infarction (PFSI), were investigated. To clarify the role of the K' conductance in these fibers, the electrophysiological activity of C has been examined in normal Purkinje fibers (NPF) and in fibers in which the K' conductance has been reduced by barium (BaPF). In NPF, C produced concentration-dependent shortening in action potential duration without change in the membrane diastolic potential. in the action potential amplitude or in the maximum upstroke ve-locity. A similar shortening was observed in PFSI and in BaPF. The shortening effect of C was more pronounced at a longer stimulation cycle length than at a short cycle length. In NPF and in PFSI. depolarizations produced by low K' (<2mM) were reversed by C. whereas there were no effects on high K+ (4&M)-induced depolarization. However BaPF were not sensitive to the hyperpolarizing effect of C. It is proposed that the electrophysiological activity of C in canine Purkinje fibers is related to an increase in the K' currents, i, and i,, in these fibers. These results also suggest that the modifications seen in PFSI could be due to a decrease in i, and a partial reduction in i,l. (supported by Manitoba Heart Foundation, we thank Beecham UK for their supply of C). 1 present address : Les Laboratoires Beecham. Rennes, France.
P134
ELECTROPHYSIOLOGICAL EFFECTS OF THE HYPOGLYCEMIC SULPHONYLUREAS ON THE HEART. G. Pogitsa, J. G. Papp, M. 2. Koltai, Z. Aranyi, G. Ballagi-Porddny, M. Jakab. Research Department, National Institute of Cardiology, Budapest, Hungary. Previous studies have demonstrated a difference among effects of various hypoglycemic sulphonylureas on myocardial contractile force and arterial blood pressure. Various sulphonylurea drugs (1 mM - 1 PM) were compared, therefore, as to their influence on the electrical activity of isolated rabbit heart preparations as well as on the arrhythmogenity of strophantinized rabbit and infarcted rat hearts. In Purkinjc fibers only glibenclamide depressed automaticity and increased conduction velocity and electrical threshold. Carbutamide, tolbutamide gliclazide and glipizide enhanced or did not influenced automaticity and decreased conduction velocity and electrical threshold. None of drugs affected resting membrane potential. All investigated compounds depressed maximal velocity of membrane depolarization and phase of partial recovery of transmembrane potential. Not any of investigated sulphonylureas influenced electrical threshold and conduction velocity in the auricle. Glibenclamide and glipizide decreased, whereas carbutamide, tolbutamide and gliclazide enhanced incidence of ventricular ectopic beats both in strophanthin treated rabbit and in infarcted rat hearts. All effects were dose-dependent, and differed also when identical molar levels were used. It follows that glibenclamide differs from other hypoglycemic drugs with respect to its influences on cardiac electrical activity.
PI35
GEUilSIS OF EARLY A?TER'?EPOL%IZATII)N IN pOl]SE ATRlAL F1RI;R.i AND ,T;, 'NHIHIT;NG AGSNTS. T-F. Liu. Department Of B;olory, Peking IlniversIty! Re:jinp, China. Ea;-!y afterdepolarizations (CADS) can be easily induced in mouse rtr-ial fibers Undel 1.5 nti; K spaI~AFS) by reduction of the concentration of I< in the superfusate. percusion, the &ADS appeared on the baclr~rourd of automatic,ity of the AF, while under 3-n d.i K treatment, the action potential Lept normal with the cycle length of driving stimlllat;on less thar. 0.5 s. Prolongation of tte (,ycle length to 1 s or more The c 3,3,4 and 5 s), EHDC appeared gradually showing its cycle lf?ngth dependence. relationship between cycle length and numder and duratiun of tripeered bursts ware inear, at least in the rarge of 1 to 5 s cycle length. Application of an extra stimulation i)T: the early repolarizatjon phase C-40 to -60 mV level) of an action potenmore than one response could be induced, tial without Exi, under 3.0 tii K superfusion, was defined as 'se<,ond plateau pivirlg a similar corfiguration of 8:riD. This phenomenon E&S could be suppr-ssed by l"lX, lidoraint,, verapamil, nifedipine and Tl+ response'. leaIcing the linear relationship bet.weeri cycle IenLth and tt,e parameters resp&ctively, rjhen t.tle EI'.D% wore inhibited by tte above agents completfly, the of E/D unchanged. cap be regarded second plateau responses disappeared concurrently. So, t,\e latt,,r It is suggested that all the ionic currentrj contributing as an indicator uf the EaD. to the plateau phase formaticn arr responsible to the FeneSiS :of EAD. '.%e
s.54