Biomedical subjects

O Binah

Publications and source records attributed to O Binah.

At least 37 records · Page 2Linked to original sources

PubMed1994

Calcium channel blockers modify electrophysiological effects induced by lytic granules from cytotoxic T lymphocytes in guinea pig ventricular myocytes.

Damage to myocytes by infiltrating cytotoxic lymphocytes, containing lytic granules and the pore-forming protein, perforin, thereof, probably contribute to the immunological rejection of the transplanted heart, to autoimmune diseases and possibly to congestive heart failure associated with myocarditis. In the present study we investigated whether electrophysiological and morphological changes induced in guinea pig ventricular myocytes by lytic granules extracted from cytotoxic T lymphocytes, are modified by L-type Ca++ channel blockers. The organic blockers, verapamil (2 microM) and nisoldipine (500 microM) were unable to prevent or inhibit any of the deleterious effects of lytic granule on action potential and myocyte morphology, and the granule-induced increase in the membrane current measured at the end of 300-msec clamp pulse. In contrast, the inorganic blockers CoCl2 (3 mM) and NiCl2 (4 mM) provided considerable protection against the granule actions mentioned above, but an equally potent Ca++ blocker, CdCl2 (3 mM) was ineffective. The protective efficacy of CoCl2 (and probably that of NiCl2) was most likely due to its capacity to reduce or block the generation by lytic granules/perforin of large-conductance (approximately 1400 pS) channels responsible for inducing Ca++ overload and cell destruction. We consider these studies of importance because they direct further studies aimed at developing effective means for attenuating cytotoxic T lymphocyte-induced tissue damage, for example during transplant rejection or in autoimmune diseases.

Action Potentials↗

PubMed1993

Hypotension in experimental cirrhosis. Is loss of vascular responsiveness to norepinephrine the cause of hypotension in chronic bile-duct-ligated dogs?

It has been postulated that one of the mechanisms of hypotension associated with cirrhosis is an attenuated responsiveness to catecholamines despite the increased activity of the sympathetic nervous system and the elevated plasma concentrations of the sympathetic neurotransmitter, norepinephrine. This abnormality was studied in a dog model of portal hypertension and cirrhosis. Twelve weeks after bile duct ligation (n = 16), intrasplenic pressure rose significantly from 6.3 +/- 0.4 to 14.6 +/- 1.6 mmHg (p < 0.05), mean arterial pressure had fallen from 106 +/- 4 to 83 +/- 8 mmHg (p < 0.01), cardiac output had risen from 3.1 +/- 0.2 to 3.8 +/- 0.8 l/min (p < 0.05) and plasma norepinephrine concentrations rose from 0.22 +/- 0.12 to 1.17 +/- 0.52 nmol/l (p < 0.05). In 7 sham-operated dogs, the changes in these 4 variables over the same period were non-significant. In vivo pressor responsiveness was tested by studying the effects of intravenous and intra-arterial infusions of norepinephrine and the non-selective beta-adrenoceptor agonist, isoproterenol. In vitro responsiveness was tested by measuring the effects of isoproterenol on the isometric twitch of isolated ventricular strips and the effects of norepinephrine on femoral, mesenteric and renal arterial rings. There was no significant change in the in vivo responses of chronic bile-duct-ligated dogs at 12 weeks compared to the preoperative assessment, or to sham-operated dogs at 12 weeks. Furthermore, there was no significant difference between the in vitro responses of ventricular strips to isoproterenol or arterial rings to norepinephrine prepared from chronic bile-duct-ligated and sham-operated dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗

PubMed1993

Mechanisms whereby lytic granules from cytotoxic T lymphocytes damage guinea pig ventricular myocytes.

During immunological rejection of the transplanted heart, cytotoxic T lymphocytes (CTL) infiltrate the myocardium and by damaging the myocytes contribute to loss of function. To address one important aspect of heart transplant rejection, we investigated in guinea pig ventricular myocytes how CTL-derived lytic granules containing the pore-forming protein perforin reduce the membrane potential (VM) and cause cell damage. The reduction in VM was biphasic; within 8.4 +/- 1.9 min VM was reduced from a control value of -78.4 +/- 1.9 mV to -69.9 +/- 3.5 mV. Subsequently, within 6.7 +/- 2.1 min VM declined to -3.4 +/- 1.2 mV, associated with a progressive contracture. Under whole cell voltage clamp, in myocytes held at their resting potential (VM = -76.2 +/- 0.9 mV), granules induced discrete inward current steps (resembling 'single channel' activity), with a mean amplitude of -86.8 +/- 1.4 pA and open times lasting from seconds up to several minutes. The mean conductance and reversal potential calculated from the linear regression analysis of the I-V relations were 1390 pS and -6.8 mV, respectively. The probable non-selectivity of these 'channels' and the resultant loss of membrane K+ selectivity can account for the reduction in VM. At the same time, opening of these pores leads to Ca2+ overload, resulting in contracture and cell damage.

Animals↗

PubMed1993

Chronotropic and dromotropic actions of acetylcholine on the developing fetal heart.

We studied the effect of acetylcholine (ACh), 1 x 10(-8) to 5 x 10(-7) M, on electrophysiologic characteristics of the isolated (Langendorf), perfused fetal canine heart. ACh induced concentration-dependent decreases in sinoatrial (SA) rate and recovery from overdrive pacing and in atrioventricular (A-V) conduction. These effects of ACh were greater in mid-gestation than late-gestation hearts. The effects of ACh were potentiated by inhibition of acetylcholinesterase by neostigmine, 1 x 10(-7) M, in the late- but not the mid-gestation fetal heart. Decreasing the pH of the perfusion solution from 7.3 to 6.8 potentiated the response to ACh of SA rate and A-V conduction more in mid- than in late-gestation hearts. The response to ACh of the late-gestation fetal canine heart is more sensitive to cholinesterase inhibition whereas the response of the mid-gestation heart is more sensitive to the action of ACh in the presence of acidosis.

Acetylcholine↗

PubMed1993

Developmental changes in the myosin composition of guinea pig ventricular muscle. Relation to thyroid state and mechanical properties.

In a variety of mammalian species, thyroid hormone regulates the contractile properties of the heart as well as the expression of the alpha and beta heavy chains of myosin. We have previously shown that the plasma levels of thyroid hormone reach a peak immediately after birth in guinea pigs and decline with maturation. We therefore studied age-related changes in the expression of the myosin heavy chains in the guinea pig ventricle in relation to the ventricular mechanical properties and the levels of thyroid hormone. The composition of the myosin heavy chains was characterized by gel electrophoresis and immunoblotting. Anti-beta-chain antibody stained equally myosins from newborns (0-5 days) and adults (75-90 days), while anti-alpha-chain positively decorated only the myosins of euthyroid newborns or of hyperthyroid adults, but not myosins of embryos, hypothyroid newborns or hypothyroid adults. Myosin of euthyroid adults was faintly stained by anti-alpha-chain. The alterations in the composition of myosin corresponded with the "thyroid state" of these groups. The plasma levels of total T3 were 24.3 +/- 2.7, 9.04 +/- 1.2 and 139.0 +/- 9.3 ng/dl (mean +/- SEM) in the euthyroid, hypothyroid and hyperthyroid adults, respectively. In euthyroid and hypothyroid newborns, the plasma levels of T3 were 56.5 +/- 11.9 and 26.5 +/- 9.8 ng/dl, respectively. Within each age group the thyroid state corresponded with maximal twitch tension (Tmax), rates of development of tension and relaxation, time to peak tension and rate of activation.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1992

Mechanism of hyperthyroidism-induced modulation of the L-type Ca2+ current in guinea pig ventricular myocytes.

The positive inotropic effects of thyroid hormone in the heart, increased force and velocity of contraction have been mostly attributed to modulation of myosin ATPase isoenzymes (V1, V2 and V3), and sarcoplasmic reticulum Ca2+ pumping activity. In addition, we have suggested that the effects on ventricular contraction result from a thyroid hormone-induced increase in L-type Ca2+ current (ICa,L). Due to the central role of ICa,L in excitation-contraction coupling, we studied mechanisms whereby thyroid hormone augments this current. Since thyroid hormone modulates adenylate cyclase activity in various tissues, we tested the hypothesis that the hormone activates adenylate cyclase, leading to increased cyclic adenosine monophosphate (cAMP) levels, protein kinase A activation, Ca2+ channel phosphorylation and increased ICa,L. We therefore stimulated or inhibited different sites along the "adenylate cyclase cascade", and measured ICa,L and isometric twitch in ventricular myocytes and papillary muscles from euthyroid and hyperthyroid guinea pigs. Our major findings were as follows. In euthyroid myocytes, 0.1 microM isoproterenol (Iso) increased ICa,L (at VM = 0 mV) from -7.04 +/- 0.72 to -22.26 +/- 1.88 pA/pF, P < 0.05, while in hyperthyroid myocytes (ICa,L = -21.48 +/- 2.94 pA/pF), Iso was ineffective. In euthyroid myocytes, intracellular application of cAMP (50 microM) was as potent as Iso, but ineffective in hyperthyroid myocytes. In hyperthyroid myocytes, a protein kinase A inhibitor (2 microM) lowered ICa,L from -26.82 +/- 1.54 to -10.17 +/- 1.70 pApF (P < 0.05), but had no effect in euthyroid myocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

PubMed1992

Immunological rejection of heart transplant: how lytic granules from cytotoxic T lymphocytes damage guinea pig ventricular myocytes.

We investigated the mechanism by which lytic granules extracted from cytotoxic T lymphocytes (CTL) damage guinea pig ventricular myocytes in order to determine whether their actions can be related to the overall immunological rejection of the transplanted heart. Granule-induced myocyte morphological changes and final destruction were preceded by shortening of action potential duration (APD) and reductions of the resting potential and the action potential amplitude. APD shortening was probably caused by a granule-induced increase in outward current (most likely non-specific). Ryanodine, which blocks Ca2+ release from the sarcoplasmic reticulum, did not interfere with the morphological and electrophysiological effects of lytic granules. Fura-2 imaging indicated that [Ca2+]i initially increased about 2-fold from 90.0 +/- 11.5 nM, while cell length decreased less than 5% from a mean value of 99.0 +/- 9.0 microns. A further increase in [Ca2+]i (greater than 10 fold) was associated with progressive contracture and destruction, suggesting that the structural damage inflicted by lytic granules is caused by [Ca2+]i overload. The results indicate that the cytocidal action of CTL-derived lytic granules may be involved in immunologically induced damage, even to the extent of rejection of the transplanted heart.

Action Potentials↗

PubMed1992

Mechanisms of ventricular arrhythmias.

Ventricular arrhythmias may result from abnormalities of impulse initiation and/or impulse propagation. The former include automatic arrhythmias, which may occur at high (normal) levels of membrane potential or at low (abnormal) levels of membrane potential. They also include triggered activity, which may result from early (occurring before complete repolarization) or delayed (occurring after complete repolarization) afterdepolarizations. Arrhythmias resulting from abnormal impulse propagation may be reentrant, determined in part by anatomic or functional conduction block, or the result of reflection. The factors determining various arrhythmogenic mechanisms are discussed.

Arrhythmias, Cardiac↗

PubMed1991

Developmental changes in ventricular action potential properties in guinea-pigs are modulated by age-related changes in the thyroid state.

Previous studies have demonstrated that in different cardiac preparations action potential duration (APD) increases with age. As in various species, thyroid hormone levels increase developmentally, and since hyperthyroidism shortens APD while hypothyroidism prolongs it, we hypothesized that developmental changes in APD result from age-related variations in the thyroid state. The hypothesis was tested by analysing ventricular action potentials and total T4 (TT4) levels in guinea-pigs in the age range of 0 days to 3 months (adult), and in hyperthyroid and hypothyroid newborns (0-5 days old). We found that APD50 increased exponentially with age with a time constant of 6.7 days, from 100.6 +/- 3.4 ms in newborns (0-5 days old) to 147.4 +/- 5.2 ms in adults (P less than 0.001). TT4 decreased exponentially with age with a time constant of 4.8 days, from 3.9 +/- 0.4 micrograms/dl in newborns to less than 1.0 microgram/dl in adults. In the age range studied, APD50 and TT4 were linearly correlated: Y = -12.13X + 142, r - 0.865. In contrast to the marked changes in APD, resting potential and action potential amplitude were age-independent, and Vmax only slightly increased with age. Alterations in the thyroid state in newborns affected ventricular action potentials as predicted by the hypothesis. In euthyroid (TT4 = 3.9 +/- 0.4 micrograms/dl), hypothyroid (TT4 = 1.6 +/- 0.4 micrograms/dl) and hyperthyroid (TT4 = 39.8 +/- 10.8 micrograms/dl) newborns, APD50 was: 100.6 +/- 3.4 ms, 117.7 +/- 4.2 ms and 63.7 +/- 7.4 ms, respectively (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

PubMed1991

Mechanical and electrophysiologic changes in rat cardiac allografts during immunologic rejection.

We studied the relationship between immunologic rejection and changes in contractility of isolated perfused papillary muscle, using heterotopically transplanted rat hearts. Rejection assessed by mononuclear cell infiltration was associated with depressed twitch amplitude and lower rates of tension development and relaxation. The relationship between maximum developed tension and [Ca2+]o was attenuated in muscle from the rejecting allografted heart, as compared with muscle of normal or isografted hearts. To determine the effects of rejection on ventricular electrophysiologic properties, we recorded transmembrane action potentials in isolated ventricular myocardium. We found that in rejecting allografted hearts the resting potential, action potential amplitude, and maximum upstroke velocity of phase zero were significantly reduced compared with normal and isografted hearts. The attenuation in the mechanical and electrophysiologic properties was largely prevented by treating the transplanted rat with anti-lymphocyte-globulin on days 0, 1, and 2 after transplantation. In summary, the present study demonstrates that immunologic rejection of the heterotopically allotransplanted rat heart is associated with marked attenuation of both mechanical and electrophysiologic properties of the ventricular myocardium.

Action Potentials↗

PubMed1991

Role of thyroid state in age-dependent cardiac effects of ouabain in guinea pigs.

We tested the hypothesis that the decrease in the thyroid state, with age, contributes to the age-related increase in myocardial responsiveness to cardiac glycosides. Thyroid hormone levels (reflecting the thyroid state): total T4 (microgram/dl) and total T3 (ng/dl) in the 3 groups of guinea pigs were (mean +/- SEM): adults (3 months old): less than 1.0 and 22.6 +/- 1.1; euthyroid newborns (0-5 days old): 3.9 +/- 0.4 and 56.5 +/- 11.9; hypothyroid newborns, (0-5 days old): 1.5 +/- 0.3 and 26.5 +/- 9.8. In euthyroid newborns, T4 and T3 levels were significantly higher than in adults (p less than 0.01 for T4 and p less than 0.05 for T3) and in hypothyroid newborns (p less than 0.05). Isometric twitch was recorded from right ventricular papillary muscles by means of a force transducer. Ouabain 10(-6) M increased isometric twitch tension in adults (tension = 0.66 +/- 0.18 g/mm2) by 123.6 +/- 18.2%, in euthyroid newborns (tension = 0.19 +/- 0.04 g/mm2) by 83.6 +/- 14.5%, and in hypothyroid newborns (tension = 0.12 +/- 0.01 g/mm2) by 170.9 +/- 33.8% (p less than 0.01). Ouabain dose-response curve in the range of 10(-7) M-0.5 x 10(-5) M was significantly different (compared by two-way ANOVA) between euthyroid newborns and hypothyroid newborns (p less than 0.01), and between euthyroid newborns and adults (p less than 0.01). Toxic effects of ouabain reflected by the generation of aftercontractions were also age related and were augmented by hypothyroidism in newborns.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1989

Thyroid hormone modulates membrane currents in guinea-pig ventricular myocytes.

Thyroid hormones have been previously shown to alter cardiac electrophysiological and mechanical properties in humans and in experimental animals. To investigate electrophysiological mechanisms responsible for some of these alterations, we recorded action potentials and membrane currents from isolated ventricular myocytes obtained from euthyroid, hypothyroid and hyperthyroid guinea-pigs. Hyperthyroidism was induced by injecting 150 micrograms/kg triiodothyronine for 8-11 days, and hypothyroidism was induced by propylthiouracil treatment for 35-45 days. We found that the slow inward current, was increased by hyperthyroidism and decreased by hypothyroidism: in euthyroid, hyperthyroid and hypothyroid myocytes peak slow inward current was (mean +/- SEM): -1.08 +/- 0.06 nA, -1.83 +/- 0.18a nA and -0.64 +/- 0.07a nA, respectively (a, p less than 0.005). In addition, the membrane potential at which peak slow inward current occurred was modified by the thyroid state and in euthyroid, hyperthyroid and hypothyroid myocytes it was (mean +/- SEM): 4.8 +/- 0.7 mV, -1.8 +/- 1.6a mV and 11.0 +/- 1.4a mV, respectively. The outward rectifying current, was also affected by the thyroid state, and in euthyroid, hyperthyroid and hypothyroid myocytes, the amplitude at VM = +60 mV was (mean +/- SEM): 0.51 +/- 0.09 nA, 1.15 +/- 0.08a nA and 0.49 +/- 0.05 nA, respectively. a, p less than 0.001 compared to euthyroid myocytes. Intraperitoneal administration of a single dose of triiodothyronine to guinea-pigs, 2 h prior to the electrophysiological experiment, increased the slow inward current amplitude, as was seen with chronic hyperthyroidism, but had no significant effect on the outward current and on the action potential.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

PubMed1989

Electrophysiological effects of thyroid hormones in guinea-pig ventricular muscle: time course and relationships to blood levels.

Chronic alterations in the thyroid state have been shown to induce marked changes in action potential characteristics, the most pronounced being shortening of action potential duration (APD) by hyperthyroidism and an increase in duration by hypothyroidism. In the present study our major objectives were to investigate the time course of the effect of thyroid hormone on action potential characteristics, to examine the relationships between thyroid hormone levels and these changes, and to test whether the electrophysiological alterations are induced both by thyroxine (T4) and triiodothyronine (T3). The major findings were that a single dose of either hormone (100 micrograms/kg) caused a marked shortening of APD, while resting potential, action potential amplitude and Vmax were unchanged. APD shortening was observed promptly after ip T4 or T3 administration, with maximal effect occurring within 2 to 3 hrs. Having determined thyroid hormone levels in the guinea-pigs used for the electrophysiological experiments, we found a close temporal association and inverse linear relationships (r = -0.82) between total T4 levels and APD. To determine whether APD shortening is induced due to a direct effect of thyroid hormone on the myocardium, euthyroid papillary muscles were superfused with 10(-6) M T3; within 3 hrs of superfusion with T3, APD was shortened from 148.8 +/- 4.7 ms to 117.7 +/- 6.4 ms (P less than 0.01), an effect blocked by the protein synthesis inhibitor cycloheximide. Our results demonstrate that thyroid hormones affect the duration of the ventricular action potential in a concentration dependent fashion. Furthermore, the study suggests that thyroid hormones affect the myocardium directly via mechanism(s) that are probably associated with thyroid hormone-related protein synthesis.

Action Potentials↗

PubMed1989

Inter-species variations in myocardial responsiveness to cardiac glycosides: possible relations to the thyroid status.

Mammalian species differ in their myocardial responsiveness to cardiac glycosides; whereas glycosides induce a marked positive inotropic effect in species such as dog, rabbit and guinea-pig, the rat myocardium is virtually insensitive. We investigated the physiological basis for this phenomenon by testing the hypothesis that the inter-species variations in the response of the myocardium to cardiac glycosides results, at least in part, from species-related differences in the "thyroid status". In the present study we focused on the toxic effects of the glycosides, and studied ouabain-induced delayed afterdepolarizations (DAD): (1) in guinea-pigs, rats and mice, which encompass a wide range of thyroid statuses, as indicated by their O2 consumption and thyroid hormone levels; (2) in guinea-pigs and rats in which the thyroid status was decreased by propylthiouracil treatment or increased by thyroxine administration (in the former species only). DAD were readily induced in guinea-pigs after 40 to 60 min superfusion with 10(-6) M ouabain and 5.4 mM Ca2+. In rats, DAD were induced only when the Ca2+ concentration was raised to 8.1 mM, but were absent in mice even after 2 h of superfusion with ouabain and 8.1 mM Ca2+. In guinea-pigs and rats (at cycle length = 500 ms), DAD amplitude was (means +/- S.E.): 2.8 +/- 0.7 mV and 1.1 +/- 0.4 mV, respectively. The slope of the DAD ascending limb (dV/dt) in guinea-pigs was 47.6 +/- 8.6 mV/s and in rats was 8.1 +/- 3.4 mV/s. In both species DAD characteristics were altered by the thyroid status. In eu-, hyper- and hypothyroid guinea-pigs, DAD amplitude and dV/dt (cycle length = 500 ms) were as follows: 2.8 +/- 0.7 mV and 47.6 +/- 8.6 mV/s; 1.2 +/- 0.4* mV and 12.6 +/- 3.9* mV/s; 7.5 +/- 0.6* mV and 204.0 +/- 18.4* mV/s, respectively (*, P less than 0.005, compared to euthyroid guinea-pigs). The occurrence of triggered beats was also dependent on the thyroid status. They occur more frequently in hypothyroidism and less frequently in hyperthyroidism. Hypothyroidism in rats augmented ouabain toxicity as reflected by an increase in DAD amplitude and dV/dt by 109% and 105%, respectively (P less than 0.05, as compared to euthyroid rats). In conclusion, we suggest that species-related differences in the thyroid status may contribute to the inter-species (as well as for the intra-species) variations in the myocardial responsiveness to cardiac glycosides.

Action Potentials↗

PubMed1988

Effect of Cs+, Li+ and Na+ on the potassium conductance and gating kinetics in the frog node of Ranvier.

The effects of monovalent internal cations Cs+, Li+ and Na+ on potassium channel conductance in the frog node of Ranvier were studied by means of the voltage clamp. As previously reported, when 10-80% of the internal K+ was replaced by one of the above cations, the steady-state current-voltage relationship was significantly modified. The main effect was a voltage-dependent attenuation of the currents. We demonstrate that the current attenuation is associated with a change in the channel gating kinetics. For small depolarizations the kinetics can be described by the usual potassium conductance activation time constant, tau n. However, under certain experimental conditions (e.g. substitution of the intracellular K+ with 10% Cs+), during larger depolarizations, stepping the membrane potential to values above 40-60 mV, the conductance develops with two time constants: tau n and a new, slower time constant that, in contrast to tau n, grows with membrane potential. These results can be explained by assuming that the cations may occupy two different sites in the channel; when the first site is occupied the channel is blocked, while occupation of the second site results in slowing of the gating kinetics in the affected channels.

Animals↗

PubMed1988

Ventricular myosin of the shrew Crocidura russula, correlation with contractile properties.

The present study demonstrates that in the shrew ventricular muscle the speed of tension development and relaxation, as well as twitch duration, are much shorter than in the guinea-pig. It also shows that ventricular myosin of the shrew has a high Ca2+-activated ATPase activity and that it is composed of alpha-type heavy chains. Namely, the native molecule is a V1 variety of myosin. These findings advance our knowledge on an as yet uncharacterized mammalian heart and further demonstrate the correlation between mechanical properties and myosin type in heart muscle.

Animals↗

PubMed1987

Effects of bile acids on ventricular muscle contraction and electrophysiological properties: studies in rat papillary muscle and isolated ventricular myocytes.

The effects of sodium salts of various bile acids on the contractile force and the electrophysiological properties of rat ventricular muscle were studied in vitro. Primary, conjugated, and secondary bile acids were studied in a concentration range of 10(-9)-10(-6) mol/l, which corresponds to concentrations found in the plasma of patients with cholestatic jaundice. In general, the bile acid induced a negative inotropic effect which was manifested as a reduction in active tension, maximum rate of tension activation, and maximum rate of tension relaxation. Twitch duration and time to peak tension were unaffected by the bile acids. The negative inotropism was associated with a reduction in ventricular action potential duration. Resting potential, action potential amplitude, and maximum upstroke velocity of phase 0 depolarization were unaffected. Voltage clamp experiments in rat ventricular myocytes demonstrated that sodium taurocholate decreased the slow inward current and slightly increased the outward potassium current. Hence, these effects on the membrane currents are probably responsible for the negative inotropic effect.

Action Potentials↗

PubMed1987

Effects of thyroid hormone on the action potential and membrane currents of guinea pig ventricular myocytes.

We studied the effects of thyroid hormone on the action potential and membrane currents recorded from enzymatically dissociated guinea pig ventricular myocytes, by means of the whole-cell recording technique. Hypothyroidism was associated with an increase in action potential duration, whereas hyperthyroidism was associated with a decrease in duration. These effects are similar to those reported in multicellular preparations. Hypo- and hyperthyroidism were also associated with a decrease and an increase, respectively, in the slope of the action potential plateau. Resting potential and action potential amplitude were unaffected by the alterations in the thyroid state. The voltage-clamp experiments revealed that as compared with euthyroid myocytes, the peak calcium current was bigger in hyperthyroid myocytes and smaller in hypothyroid myocytes. The potassium outward current (at a membrane potential = 50 mV) was of similar amplitude in hypo- and euthyroid myocytes and bigger in hyperthyroid myocytes. Our major conclusion is that thyroid hormones regulate the amplitude of the calcium current and that this effect may be responsible in part for the modulation of myocardial contractility by thyroid hormones.

Action Potentials↗