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N Sperelakis

Publications and source records attributed to N Sperelakis.

At least 37 records · Page 2Linked to original sources
PubMed1997

Tyrosine kinase inhibitor, genistein, inhibits macroscopic L-type calcium current in rat portal vein smooth muscle cells.

The effect of genistein, a specific tyrosine kinase inhibitor, was tested on the slow (L-type) Ca2+ current (ICa(L)) of vascular smooth muscle cells from freshly isolated rat portal vein, using whole-cell voltage clamp. To isolate ICa(L), the pipette contained high Cs+ and the bath contained 140 mM tetraethylammonium (TEA) to block K+ currents. Bath application of genistein decreased ICa(L) in a concentration-dependent manner within 3-6 min. The concentration for half-maximal inhibition (IC50) was 54.9 microM (at a holding potential of -40 mV). At a concentration of 300 microM, genistein produced nearly complete inhibition of ICa(L). The inhibitory effect of genistein was not reversed after washout for up to 5 min. The potential for half-inhibition (V1/2) of the steady-state inactivation curve for ICa(L) was shifted to the left by genistein (10.6 mV at 50 microM), suggesting that genistein exerts a voltage-dependent block. Superfusion with daidzein, an inactive analog of genistein, had no inhibitory effect on ICa(L) at concentrations as high as 300 microM. These results may suggest that the L-type Ca2+ channels in vascular smooth muscle cells are possibly modulated by endogenous tyrosine kinase activity. That is, tonic phosphorylation by tyrosine kinases maintains the Ca2+ channels in an available state for activation by depolarization. Thus, the vascular tone may be controlled by tyrosine kinase activity.

Animals↗
PubMed1997

Regulation of Ca2+ channel currents by intracellular ATP in smooth muscle cells of rat mesenteric artery.

Regulation of L-type Ca2+ channels of vascular smooth muscle (VSM) cells by adenosine 3',5'-cyclic monophosphate (cAMP)-dependent and guanosine 3',5'-cyclic monophosphate (cGMP)-dependent phosphorylation, which requires Mg2+ATP as a phosphate donor, has been reported (T. Ishikawa, J. R. Hume, and K. D. Keef. Circ. Res. 73: 1128-1137, 1993; Z. Xiong, N. Sperelakis, and C. Fenoglio-Preiser. J. Vasc. Res. 31: 271-279, 1994), and regulation by ATP has been demonstrated (Y. Ohya and N. Sperelakis. Circ. Res. 64: 145-154, 1989). However, it has not been elucidated whether the regulation by ATP is mediated by a mechanism that is distinct from phosphorylation. In the present study, we examined the effects of intracellularly perfused ATP on Ca2+ channel currents of VSM cells isolated from rat mesenteric arteries using a whole cell voltage clamp combined with an intracellular perfusion technique. Ba2+ currents (I(Ba)) through Ca2+ channels were evoked by depolarizing pulses from a holding potential of -80 mV with 130 mM Cs+ in the pipette and 100 mM Ba2+ in the bath. The decrease in the ATP concentration (from 5 to 0.1 mM) in the pipette caused a 45 +/- 5% (n = 8) reduction of maximal I(Ba) obtained at +40 mV within 10 min. The dose-response relation between I(Ba) and ATP showed a dissociation constant of 0.53 mM ATP. This concentration is much higher than that usually required for phosphorylation (e.g., few micromolar). Increase in the ATP (from 0.1 to 5 mM) caused an enhancement of maximal I(Ba) by 57 +/- 10% (n = 6), and this enhancement was not prevented in the presence of 30 microM H-7, a nonspecific inhibitor of protein kinases, or 1 microM protein kinase inhibitor, an inhibitor protein of cAMP-dependent protein kinase. These results indicate that slow Ca2+ channels in VSM cells are regulated by intracellular ATP, independently of phosphorylation, implying a direct regulatory action, such as a requirement for ATP binding to the inner surface of the channel, to exhibit activity.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1997

The novel calcium sensitizer levosimendan activates the ATP-sensitive K+ channel in rat ventricular cells.

Levosimendan, a new Ca++-sensitizing and positive inotropic agent, was reported to act as a coronary vasodilator and protect ischemic myocardium. To elucidate the mechanisms of these actions, the possible electrophysiological effects of levosimendan on isolated rat ventricular cells were examined by the patch-clamp technique with whole-cell and single-channel recordings. Levosimendan (3 and 10 microM) markedly shortened action potential duration and activated an outward current at potentials positive to -70 mV. The increased current was abolished by glibenclamide, a blocker of the ATP-sensitive K+ (K[ATP]) current. Stimulation of K[ATP] current was dose dependent, with an EC50 value of 4.7 microM; a maximal effect occurred at 30 microM. The L-type Ca++ current was not affected by levosimendan (0.2-10 microM). In single-channel current recording in open cell-attached patches, K[ATP] channels, which had been inhibited by 0.3 mM ATP, were activated by levosimendan. However, levosimendan did not stimulate the K[ATP] channels that exhibited high spontaneous activity in ATP-free solution. Levosimendan also could not stimulate K[ATP] channels that had rundown in ATP-free solution. However, levosimendan could stimulate rundown K[ATP] channels that were reactivated by nucleotide diphosphates. K[ATP] channels inhibited by 0.5 mM AMP-PNP, a nonhydrolyzable ATP analog, were not stimulated by levosimendan; however, the channels were stimulated by levosimendan in the presence of 30 to 50 microM ADP. Levosimendan stimulates cardiac K[ATP] channels that are suppressed by intracellular ATP. It appears that levosimendan acts synergistically with nucleotide diphosphates. These properties of levosimendan may help protect ischemic myocardium because activation of K[ATP] channels by levosimendan would likely occur in ischemic regions in which intracellular ADP concentration is increased and intracellular ATP concentration is decreased.

Action Potentials↗
PubMed1997

Tyrosine kinases modulate the activity of single L-type calcium channels in vascular smooth muscle cells from rat portal vein.

In a previous study, we demonstrated that extracellular application of the tyrosine kinase inhibitor genistein produced a dose-dependent inhibition of the macroscopic slow (L-type) Ca2+ currents of vascular smooth muscle (VSM) cells, and that daidzein, an inactive analog of genistein, had no such effect. These results suggested that the L-type Ca2+ channels in VSM cells may be modulated by endogenous tyrosine kinase activity. To confirm and extend those findings, the effect of genistein on the activity of single Ca2+ channels was examined in freshly isolated single VSM cells from rat portal vein, using the cell-attached patch-clamp technique. The pipette solution contained 90 mM Ba2+ as charge carrier and 0.5 microM Bay K 8644 (to enhance basal activity of the channels), and the bath contained 140 mM KCl to "zero" the resting membrane potential. Depolarizing pulses to 0 mV, from a holding potential of -80 mV, elicited inward unitary currents that were blocked by 1 microM nifedipine (n = 6). The slope conductance of the unitary Ca2+ currents gave a value of 21.5 +/- 0.4 pS (n = 9) for the Ca2+ channels. Bath application of genistein (50 microM) did not change the unit amplitude and slope conductance: the conductance in the presence of genistein was 22.2 +/- 0.5 pS (n = 6). However, compared with controls, the activity of single Ca2+ channels was significantly inhibited by genistein in a dose-dependent fashion. The ensemble-averaged currents were decreased by 48.4 +/- 11.2% with 50 microM genistein; 100 microM genistein inhibited the Ca2+ currents by 76.8 +/- 11.8%. The open probability (NPo) was decreased by 50 microM genistein from 0.24 +/- 0.09 to 0.11 +/- 0.07. Single-channel kinetic analysis showed that genistein decreased the mean open time and prolonged the mean closed time. The inhibitory effect of genistein on the Ca2+ channel activity occurred within 3 min, and it could be reversed by washout within 3-5 min. Daidzein, in concentrations up to 300 microM, produced no change in the activity of the single Ca2+ channels. These results demonstrate that genistein inhibits the activity of the L-type Ca2+ channels in VSM cells, suggesting that the availability of the channels for voltage activation may be maintained through tonic tyrosine kinase phosphorylation.

Animals↗
PubMed1997

Cyclic GMP-dependent protein kinase regulates the L-type calcium current in rat ventricular myocytes.

This study aimed to elucidate the mechanism of cyclic granosine monophosphate (cGMP)-dependent protein kinase (PK-G) regulation of the L-type Ca2+ channel current (ICa(L) in young rat ventricular myocytes using whole-cell voltage clamp with internal perfusion. ICa(L) was usually elicited from a holding potential (HP) of -40 mV. Stimulated ICa(L) (by 2 microM isoproterenol) was inhibited to the basal level by internal perfusion with 50 nM PK-G (activated by 8Br-cGMP, 0.1 microM). Basal ICa(L) (non-stimulated through the cyclic adenosine monophosphate (cAMP)/PK-A pathway) was also inhibited to various degrees (large, medium, or small) by internal application of PK-G (25 nM). The average inhibition was 42.1%, and there were no differences in the inhibition during development. The inhibition by PK-G was blocked by the PK-G substrate peptide (300 microM) and by heart-inactivation of PK-G. The inhibited ICa(L) was reversed by ISO (seven of eight cells). When an HP of -80 mV was used, the inhibition produced by PK-G was much less. The inhibitory effects of PK-G were not mediated by activating phosphodiesterases or protein phosphatases, but most likely by a direct phosphorylation of the Ca2+ channel or associated regulatory protein. The inhibitory effect of PK-G may be explained by a balance between the activities of PK-A and PK-G in regulating the slow Ca2+ channels at two separate sites.

Animals↗
PubMed1996

Differences in isoproterenol stimulation of Ca2+ current of rat ventricular myocytes in neonatal compared to adult.

The developmental changes in the isoproterenol stimulation of the L-type calcium current (ICa(L)) were studied in freshly isolated neonatal (3-5-day-old) and adult (2-3-month-old) rat ventricular myocytes using whole-cell voltage clamp (at room temperature). ICa(L) was measured as the peak inward current at a test potential of +10 mV (or +20 mV) by applying a 300 ms pulse from a holding potential of -40 mV. The pipette solution was Cs(+)-rich and Ca(2+)-free. The external solution was Na(+)-free and K(+)-free. Isoproterenol stimulated ICa(L) in a dose-dependent manner. The concentrations of isoproterenol for half-maximal effect were 6.8 nM in neonatal and 13.3 nM in adult. The maximal stimulation of ICa(L) was 147 +/- 14% in neonatal and 97 +/- 7% in adult. The steady-state inactivation curves were not affected by isoproterenol, whereas the steady-state activation curve was shifted to the left in both neonatal and adult. Forskolin (10 microM) increased ICa(L) by 105 +/- 10% in neonatal and 90 +/- 12% in adult. After stimulating ICa(L) by forskolin, the addition of isoproterenol produced a further increase of ICa(L) by 99 +/- 27% in neonatal, but only by 19 +/- 3% in adult. The presence of an inhibitor of cAMP-dependent protein kinase in the pipette did not affect this marked difference between neonatal (87 +/- 23%) and adult (11 +/- 8%). We conclude that, in rat ventricular myocytes, (1) stimulation of ICa(L) by the beta-adrenoceptor agonist, isoproterenol, is already fully developed in the neonatal stage and actually decreases during development; (2) there is evidence for a cAMP-independent stimulation of Ca2+ channels by isoproterenol, and this is greater in neonatal than in adult. We believe that the cAMP-independent pathway is the direct pathway mediated by Gs alpha protein.

Adrenergic beta-Agonists↗
PubMed1996

Na+/Ca2+ exchange current: lack of effect of taurine.

The intracellular taurine content is very high in some types of cells, including myocardial cells, and taurine becomes depleted in failing hearts. The effect of taurine on inward (forward) and outward (reversal) Na+/Ca2+ exchange current (INa/Ca) was examined in freshly isolated rat (11-20-day-old) ventricular cells using whole-cell voltage clamp. INa/Ca was evoked by a 300 ms ramp hyperpolarizing pulse at a rate of 0.67 V/s (from +60 to -140 mV) from a holding potential of -40 mV. Under the condition of 500 nM Ca2+ in the pipette, when the bath solution was changed from 150 mM Li+ to 150 mM Na+, an inward INa/Ca was initiated. On the other hand, under the condition of 50 mM Na+ and 56 nM Ca2+ in the pipette, when the bath solution was changed from Na(+)-free, Ca(2+)-free solution to Na(+)-free, 2 mM Ca2+, an outward INa/Ca was initiated. Both inward and outward INa/Ca were completely blocked by 5 mM Ni2+, helping to identify the current as INa/Ca. Forward and reversal INa/Ca was measured in the absence (control) and presence of 30 mM taurine added to the bath. The current densities (pA/pF) of inward INa/Ca at -50 mV were 0.75 +/- 0.12 in control and 0.73 +/- 0.11 in presence of 30 mM taurine. Outward INa/Ca at +50 mV were 0.73 +/- 0.08 in control and 0.65 +/- 0.02 in 30 mM taurine. There were no significant differences between control and taurine for both inward and outward INa/Ca. Therefore, the various effects of taurine reported on the heart are not caused by a direct effect of taurine on Na/Ca exchange.

Animals↗
PubMed1996

Amino acid substitutions in the rat Na+, K(+)-ATPase alpha 2-subunit alter the cation regulation of pump current expressed in HeLa cells.

1. To study the functional role of negatively charged amino acids (E327 and D925) located in the transmembrane region of the rat alpha 2-isoform of the Na+, K(+)-ATPase (rat alpha 2*) in ion transport, the effects of mutations on external K+ dependence and internal Na+ dependence of pump currents were assessed by the patch-clamp technique in combination with a system for rapid solution changes. 2. Amino acid residues were replaced by glutamine (E327Q) or leucine (D925L) and were introduced into rat alpha 2* cDNA which encodes a ouabain-resistant isoform. These mutant enzymes were stably expressed in HeLa cells. The endogenous ouabain-sensitive HeLa cell Na+, K(+)-ATPase activity was selectively inhibited by 1 microM ouabain present in both the growing media and the assay solution. 3. External K(+)- and internal Na(+)-dependent pump activation was observed in all cells expressing rat alpha 2*, E327Q or D925L; however, the apparent affinities were significantly reduced by the mutations. 4. In E327Q, the activation of pump current was slightly slower than for rat alpha 2*, whereas the deactivation rate was faster. In contrast, D925L produced pump current having dramatically slower activation and deactivation kinetics. 5. These results indicate that these negatively charged amino acids (E327 and D925) are important in cation-induced conformational changes of the protein, which are intermediate steps in the pump mechanism.

Amino Acid Sequence↗
PubMed1996

Genistein inhibition of fast Na+ current in uterine leiomyosarcoma cells is independent of tyrosine kinase inhibition.

Possible regulation of fast Na+ channels by tyrosine kinase was examined in human uterine smooth muscle cell line, using whole-cell voltage clamp (at a holding potential of - 90 mV). Bath application of genistein, an inhibitor tyrosine kinase, decreased the fast Na+ current (INa(f)) dose-dependently. The maximal inhibition of INa(f) was 98%, and the concentration for half-maximal inhibition (IC50) was 9 microM. The effect of genistein was rapidly reversible. Daidzein, an inactive analog of genistein, had a similar inhibitory effect on INa(f). These results suggest that the fast Na+ channels in uterine sarcoma cells may be directly blocked by genistein and daidzein, i.e., their effect may be independent of tyrosine kinase inhibition.

Electrochemistry↗
PubMed1996

Inhibition of L-type calcium current in rat ventricular cells by the tyrosine kinase inhibitor, genistein and its inactive analog, daidzein.

Effects of genistein, a specific inhibitor of tyrosine kinase, on the L-type Ca2+ channels were examined in freshly isolated young (days 10-18) rat ventricular cells using the whole-cell patch-clamp technique. Bath application of genistein decreased the L-type Ca2+ current [I(Ca(L))] in a concentration-dependent manner. The maximal inhibition of I(Ca(L)) was about 40% (attained at concentrations above 100 microM); the concentration for half-inhibition (IC50) was 11 microM. The effect of genistein (applied for about 5 min) was poorly reversible after washout for up to 5 min. The potential for half-inhibition (Vh) of the steady-state inactivation curve was shifted in the negative direction by 7 mV (at 100 microM) by genistein, and the slope factor was also slightly changed; the activation curve was not affected. Daidzein, which is structurally related to genistein, but has little inhibitory effect on tyrosine kinase activity (of the EGF receptor), unexpectedly had almost the same inhibitory effect on I(Ca(L)). These observations suggest two possibilities for modulation of I(Ca(L)) in rat ventricular cells by genistein: (a) phosphorylation of the slow Ca2+ channels by tyrosine kinase; and (b) direct inhibition of the slow Ca2+ channels (i.e. independent of inhibition of tyrosine kinase activity).

Action Potentials↗
PubMed1996

Modulation of Ca2+ and Na+ transport by taurine in heart and vascular smooth muscle.

Using the whole-cell voltage clamp technique, taurine was found to affect different types of various ionic currents including T and L-type Ca2+ currents, slow Na+ and fast Na+ currents as well as the delayed outward K+ current. Also, in normal situations, taurine had no effect on the Na(+)-Ca2+ exchange current. The effect of taurine on the different types of ionic currents appears to depend on [Ca2+]o and [Ca2+]i and may also vary according to the tissue or cell type studied. Using standard Ca2+ imaging techniques, short-term exposure (10 to 20 min) of single heart cells and aortic vascular smooth muscle cells was found to increase total intracellular free Ca2+ in a dose-dependent manner. However, using 3-dimensional Ca2+ and Na+ imaging techniques, long-term exposure of heart and vascular smooth muscle cells to taurine was found to decrease both nuclear and cytosolic Ca2+ without significantly changing either nuclear or cytosolic Na+ levels. Long-term exposure to taurine was found to prevent cytosolic and nuclear increases of Ca2+ induced by permanent depolarization of heart cells with high [K+]o. This preventive effect of taurine on nuclear Ca2+ overload was associated with an increase of both cytosolic and nuclear free Na+. Thus, the effect of long-term exposure to taurine on intranuclear Ca2+ overload in heart cells seems to be mediated via stimulation of sarcolemma and nuclear Ca2+ outflow through the Na(+)-Ca2+ exchanger.

Animals↗
PubMed1996

Developmental changes in beta-adrenergic and muscarinic modulations of Ca2+ currents in fetal and neonatal ventricular cardiomyocytes of the rat.

Developmental changes of the beta-adrenergic and muscarinic modulations acting on the slow Ca2+ channels in rat ventricular cardiomyocytes were investigated using Ba2+ as the charge carrier (IBa(L)). Single cardiomyocytes from fetal and neonatal rats were freshly isolated, and currents were recorded by whole-cell voltage clamp in Na(+)-free, K(+)-free external solution. Basal current densities showed a large increase between fetal days 15 and 18, and a small decrease after fetal day 20. The ability of isoproterenol (ISO, 1 microM) to enhance IBa(L) increased dramatically between fetal days 18 and 20, and remained almost constant thereafter during the neonatal period. The ability of forskolin (FOR, 10 microM) to stimulate IBa(L) also increased markedly between fetal day 18 and neonatal day 1. Carbachol (CCh), in a dose-dependent manner, reversed the stimulation of the IBa(L) produced by ISO in neonatal cardiomyocytes. The IC50 values for CCh inhibition of IBa(L) was almost the same on all neonatal days tested (neonatal days 1, 5 and 10). The results indicate that there are developmental changes in beta-adrenergic modulation of IBa(L) in the late fetal period, including a large jump in sensitivity to ISO on about fetal day 19. These findings are consistent with the steep increase in number of beta-adrenergic receptors that occurs between fetal days 18 and 20 (Kojima, Sperelakis & Sada, 1990a: Kojima, Ishima, Taniguchi, Kimura, Sada & Sperelakis, 1990C).

Adrenergic beta-Agonists↗
PubMed1996

Stimulation of Ca2+ current by phorbol esters in rat myometrial cells is dependent on intracellular Ca2+ concentration.

The effects of phorbol esters on the L-type Ca2+ current (ICa(L)) were investigated using nystatin-perforated patch and standard whole-cell voltage clamp in uterine smooth muscle cells isolated from late-pregnant rats. Using nystatin-perforated patch to maintain the integrity of the cytosol components, phorbol 12-myristate 13-acetate (PMA, 300 nM) increased ICa(L). When the standard whole-cell voltage clamp was used, the effect of PMA was dependent on the Ca2+ concentration in the pipette solution: PMA enhanced ICa(L) at pCa 6 and pCa 7 but not at pCa 10 or pCa 8. The effect of PMA was reversed by a selective inhibitor of protein kinase C, calphostin-C (500 nM). It is concluded that phorbol esters stimulate ICa(L) in uterine muscle cells and that the isoform of protein kinase C involved in this effect is Ca2+ dependent. This mechanism may be involved in the regulation of uterine contraction during pregnancy.

Animals↗
PubMed1996

Relaxation of subarachnoid hemorrhage-induced spasm of rabbit basilar artery by the K+ channel activator cromakalim.

BACKGROUND AND PURPOSE: Cerebral vasospasm resulting from subarachnoid hemorrhage (SAH) is refractory to most vasodilators. However, despite evidence that a mechanism underlying the vasospasm may be smooth muscle cell membrane depolarization resulting from decreased K+ conductance, the ability of K+ channel activators to relax the spasm has not been thoroughly investigated. The purpose of this study, therefore, was to investigate whether K+ channel activation selectively relaxes SAH-induced vasospasm. METHODS: Three days after SAH in the rabbit, relaxation of the basilar artery in response to the K+ channel activator cromakalim as well as to staurosporine (protein kinase C antagonist), forskolin (adenylate cyclase activator), and sodium nitroprusside (guanylate cyclase activator) was measured in situ with the use of a cranial window. Relaxation in response to these agents was also investigated in control vessels contracted with serotonin. Membrane potential of the smooth muscle cells of the basilar artery from SAH and control rabbit was measured in vitro with the use of intracellular microelectrodes. RESULTS: Cromakalim completely relaxed the SAH-induced spastic basilar artery, while staurosporine, forskolin, and sodium nitroprusside were significantly less efficacious. In contrast, sodium nitroprusside and forskolin were more efficacious relaxants in serotonin-contracted control vessels than in SAH vessels. The K+ channel blocker glyburide and high [K+] prevented cromakalim-induced relaxation. Glyburide did not inhibit forskolin-induced relaxation of serotonin-contracted control vessels. Cromakalim concentration-dependently repolarized spastic basilar artery smooth muscle cells, and the repolarization was prevented by glyburide. CONCLUSIONS: These results suggest that K+ channel activation selectively relaxes SAH-induced vasospasm. We speculate that the ability of K+ channel activators to selectively relax the spasm may be due, at least in part, to the underlying inhibition of K+ channels after SAH.

Animals↗
PubMed1996

Action potential duration-stabilizing action of taurine in guinea pig ventricular myocytes.

To examine taurine actions on the rate of repolarization of action potentials (AP), L-type Ca2+ (ICa), late outward K+ (Ik) and the inward rectifier currents as affected by the external Ca2+ concentrations ([Ca2+]o), whole-cell voltage-clamp and current-clamp experiments were conducted in guinea pig ventricular myocytes. At a high (3.6 mM) [Ca2+]o, 10 mM taurine suppressed both ICa and IK, shortened AP duration and decelerated the rate (-dV/dt) of terminal repolarization of AP. In contrast, at a low (0.9 mM) [Ca2+]o, taurine intensified both ICa and IK, lengthened AP duration and accelerated -dV/dt. However, at either [Ca2+]o, the resting membrane potential was slightly hyperpolarized, and the inward rectifier, current examined by the ramp-pulse protocol remained unaffected by taurine. Taurine is suggested to maintain a stable AP duration by altering the inward Ca2+ and IK in the opposite directions, depending on [Ca2+]o. The relevance of the stabilizing action of taurine on the AP duration to its reported anti-arrhythmic efficacies is discussed.

Action Potentials↗
PubMed1996

Kinetic mechanism of Na+ channel depression by taurine in guinea pig ventricular myocytes.

To examine effects of taurine on the kinetics of the Na+ channel current (I(Na)), action potentials and whole-cell Na+ currents were recorded from single ventricular myocytes of guinea pigs. Kinetic parameters for the activation and inactivation of I(Na) were determined in accordance with the first-order kinetic model. Changes in the kinetic parameters were assessed before and after taurine exposure (5-50 mM). While taurine at concentrations higher than 10 mM decreased the peak I(Na) by ca. 15%, the agent did not alter the reversal potential and the maximum Na+ conductance (GNa). Taurine shifted the steady-state inactivation (h(infinity)) curve toward the negative potential direction and decreased the slope of h(infinity). Concomitantly, the slope of the steady-state activation (m(infinity)) was also slightly decreased and the rate of inactivation in the large potential region (-40 to -30 mV) slightly increased, whereas the rate of the activation appeared to remain unchanged. It is suggested that taurine alters the surface charge of the membrane and reduces the number of charges moving upon activation and inactivation of channels, thereby reducing I(Na).

Action Potentials↗
PubMed1996

Suppression of channel conductance by diacetyl monoxime in guinea pig and embryonic chick cardiomyocytes.

AIM: To examine the effects of diacetyl monoxime (DAM), and putative dephospohrylating agent, on conductance of the cardiac Ca, Na, and K channels. METHODS: The Ca (ICa), Na (INa), and K (IK) currents were recorded in single ventricular myocytes from guinea pigs and chick embryos before and after addition of DAM using the whole-cell voltage-clamp technique. RESULTS: DAM 10 mmol.L-1 reduced rapidly the amplitudes of ICa (by about 30%), INa (by about 25%), and IK (by 25%-50%) without alterations of the voltage-dependence. CONCLUSION: DAM was a channel inhibitor of the unique type having nonselective phosphatase activities.

Animals↗