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Calcium current and background current activation in L-triiodothyronine(T3) loaded ventricular myocytes of the rabbit
J Mol Cell Cardiol 24 (Supplement IV) (1992)
P-13
INFLUENCE SURFACE
OF MODULATION ACIDIFICATION AND
OF ATP-REGULATED K+ ACCUMULAllON
K+ CHANNELS ON IN MAMMALIAN CARDIAC
ISCHAEYIA-INDUCED TISSUE
Bert Vanheel, Alex de Hemptinne. Laboratory of Normal and Pathological Physiology, University of Gent, De Pintelaan 185, B-9ooo Gent, Belgium. We investigated in isolated guinea-pig papillary muscle the effect of pre-exposure to inhibitors or activators of the ATP-regulated K+ (KAm) channels on the ischaemia-induced changes of the action potential, the extracellular pH and K+ concentration. During conditions of superfusion arrest, causing acidiication by accumulation of metabolic acids, the simultaneously developing hypoxia primarily induces shortening of the action potential duration (APD) and accumulation of extracellular K+ with associated membrane depolarization. These last changes do not occur if hypoxia is prevented in the condition of superfusion arrest. Glibenclamide (10-50 uM) slowed the decrease of the APD in 40 % of the muscles, while the increase of ;r, was only moderately influenced. In the presence of 200 uM of the K Am channel inhibiir, the extracellular K+ accumulation was not significantly different from the control. The presence of tolbutamide (1 mM) had no effect on the decrease of APD, but moderately slowed the increase of a*,+ Superfusion with lemakafim (BRL 33227) decreased APD dose-dependently. In papillary muscles in which APD was decreased by pm-superfusion with lemakatim. a subsequent ischaemic episode did not accelerate but rather delayed the rise of a=,+ We conclude that, in our model of simulated ischaemia, surface acidification and K+ accumulation are relatively insensitive to dassical KAm channel inhibition or activation preceding the ischaemic insult. The severity of the developing hypoxia in the condition of superfusion arrest, modulation of the [ATP], decline and [ADPli rise by these substances, and modulation of the sulfonylurea binding to the KATp channel protein, all could underly this relative insensitivity.
P-14 CALCIUM
CURRENT AND BACKGROUND CURRENT ACTIVATION IN L-TRIIODOTHYRONINE(T,) LOADED VENTRICULAR MYOCYTES OF THE RABBIT Jin Han*, Eui Y Kim*, Chae H Leem, In S So **, Won K Ho, Yung E Enrm. Department of Physiology, College of Medicine, Seoul National University, Inje University*, Inha University**, Korea. Permissive action of thyroid hormone was investigated in rabbit ventricular myocytes using whole cell patch clamp technique. Single cells were isolated by Langendorff perfusion with collagenase. Cardiac myocytes were incubated in KB medium containing 1 PM L-triiodothyronine() at 4 for two to four hours. Calcium current (I&) was increased in Tg loaded cells, however, the shape of I-V curve and reversed potential did not altered. Cyclic AMP, cyclic GMP, isoprenaline and IBMX increased I, in euthyroid and hyperthyroid conditions, and acetylcholine blocked the increase of 1, in T3 loaded cells. The effect of CAMP on I,-, in T3 loaded cells was much larger than that of cGMP, but the effect of cGMP on ICa was larger than that of CAMP in control cells. Background current induced by isoprenaline also increased in T3 loaded cells. From the above results it is suggested that the permissive action of thyroid hormone to catecholamine could induce arrythmia through the increase of 1, and background current..
p-15
OPIATES CALCIUM
AND “CARDIOEXCITATORY” EXCHANGE IN CARDIAC
TETRAPEPTIDES SARCOLEMMA VESICLES.
INHIBlT
SODIUM-
Daniel Kbananshvili. Department of Biochemistry, Welzmann Institute of Science, Rehovot 76100, P.O.B. 26, Israel. The present study shows that opiates and FMRFa-related peptides can specifically and completely inhibit Na/Ca exchange and its partial reaction the Ca/Ca exchange in cardiac sarcolemma vesicles. Non-opioid d-stereoisomers (dextrorphan, Mr 1542MS, WIN 44,441-3) display effects similar to their 1-opioid isomers (levorphanol, Mr 1543MS, WIN 44,441-2). Both agonists and antagonists exert the same inhibitory potency suggesting that the opiate-induced inhibition of Na/Ca exchange mav not be mediated by opiate receptors. Since the FMRFa-like peptides were suspected to be an endogenous ligand for putative “opiate-like” receptors, the effect of more than twenty relevant peptides were tested on the exchange modes. The peptides show a wide range of inhibitory potency (IC, = 10’3-10%I). They inhibit both, the Nq-dependent “Ca-uptake and Nq-dependent “Ca-efflux, suggesting that the bidirectional movements of ions are altered. Opiates and FMRFa-like peptides display very similar kinetic effects on Na/Ca and Ca/Ca exchanges. Dextrorphan and FLRFa are mutually exclusive inhibitors, suggesting that they may bind to the same site. This putative site could be located either on the Na/Ca exchanger itself, or on an unidentified receptor. It is proposed that endogenous FMRFa-related peptides may control Ca-homeostasis via the Na/Ca exchange. s.40
P-13
INFLUENCE SURFACE
OF MODULATION ACIDIFICATION AND
OF ATP-REGULATED K+ ACCUMULAllON
K+ CHANNELS ON IN MAMMALIAN CARDIAC
ISCHAEYIA-INDUCED TISSUE
Bert Vanheel, Alex de Hemptinne. Laboratory of Normal and Pathological Physiology, University of Gent, De Pintelaan 185, B-9ooo Gent, Belgium. We investigated in isolated guinea-pig papillary muscle the effect of pre-exposure to inhibitors or activators of the ATP-regulated K+ (KAm) channels on the ischaemia-induced changes of the action potential, the extracellular pH and K+ concentration. During conditions of superfusion arrest, causing acidiication by accumulation of metabolic acids, the simultaneously developing hypoxia primarily induces shortening of the action potential duration (APD) and accumulation of extracellular K+ with associated membrane depolarization. These last changes do not occur if hypoxia is prevented in the condition of superfusion arrest. Glibenclamide (10-50 uM) slowed the decrease of the APD in 40 % of the muscles, while the increase of ;r, was only moderately influenced. In the presence of 200 uM of the K Am channel inhibiir, the extracellular K+ accumulation was not significantly different from the control. The presence of tolbutamide (1 mM) had no effect on the decrease of APD, but moderately slowed the increase of a*,+ Superfusion with lemakafim (BRL 33227) decreased APD dose-dependently. In papillary muscles in which APD was decreased by pm-superfusion with lemakatim. a subsequent ischaemic episode did not accelerate but rather delayed the rise of a=,+ We conclude that, in our model of simulated ischaemia, surface acidification and K+ accumulation are relatively insensitive to dassical KAm channel inhibition or activation preceding the ischaemic insult. The severity of the developing hypoxia in the condition of superfusion arrest, modulation of the [ATP], decline and [ADPli rise by these substances, and modulation of the sulfonylurea binding to the KATp channel protein, all could underly this relative insensitivity.
P-14 CALCIUM
CURRENT AND BACKGROUND CURRENT ACTIVATION IN L-TRIIODOTHYRONINE(T,) LOADED VENTRICULAR MYOCYTES OF THE RABBIT Jin Han*, Eui Y Kim*, Chae H Leem, In S So **, Won K Ho, Yung E Enrm. Department of Physiology, College of Medicine, Seoul National University, Inje University*, Inha University**, Korea. Permissive action of thyroid hormone was investigated in rabbit ventricular myocytes using whole cell patch clamp technique. Single cells were isolated by Langendorff perfusion with collagenase. Cardiac myocytes were incubated in KB medium containing 1 PM L-triiodothyronine() at 4 for two to four hours. Calcium current (I&) was increased in Tg loaded cells, however, the shape of I-V curve and reversed potential did not altered. Cyclic AMP, cyclic GMP, isoprenaline and IBMX increased I, in euthyroid and hyperthyroid conditions, and acetylcholine blocked the increase of 1, in T3 loaded cells. The effect of CAMP on I,-, in T3 loaded cells was much larger than that of cGMP, but the effect of cGMP on ICa was larger than that of CAMP in control cells. Background current induced by isoprenaline also increased in T3 loaded cells. From the above results it is suggested that the permissive action of thyroid hormone to catecholamine could induce arrythmia through the increase of 1, and background current..
p-15
OPIATES CALCIUM
AND “CARDIOEXCITATORY” EXCHANGE IN CARDIAC
TETRAPEPTIDES SARCOLEMMA VESICLES.
INHIBlT
SODIUM-
Daniel Kbananshvili. Department of Biochemistry, Welzmann Institute of Science, Rehovot 76100, P.O.B. 26, Israel. The present study shows that opiates and FMRFa-related peptides can specifically and completely inhibit Na/Ca exchange and its partial reaction the Ca/Ca exchange in cardiac sarcolemma vesicles. Non-opioid d-stereoisomers (dextrorphan, Mr 1542MS, WIN 44,441-3) display effects similar to their 1-opioid isomers (levorphanol, Mr 1543MS, WIN 44,441-2). Both agonists and antagonists exert the same inhibitory potency suggesting that the opiate-induced inhibition of Na/Ca exchange mav not be mediated by opiate receptors. Since the FMRFa-like peptides were suspected to be an endogenous ligand for putative “opiate-like” receptors, the effect of more than twenty relevant peptides were tested on the exchange modes. The peptides show a wide range of inhibitory potency (IC, = 10’3-10%I). They inhibit both, the Nq-dependent “Ca-uptake and Nq-dependent “Ca-efflux, suggesting that the bidirectional movements of ions are altered. Opiates and FMRFa-like peptides display very similar kinetic effects on Na/Ca and Ca/Ca exchanges. Dextrorphan and FLRFa are mutually exclusive inhibitors, suggesting that they may bind to the same site. This putative site could be located either on the Na/Ca exchanger itself, or on an unidentified receptor. It is proposed that endogenous FMRFa-related peptides may control Ca-homeostasis via the Na/Ca exchange. s.40