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Y Shimoni

Publications and source records attributed to Y Shimoni.

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

Thyroid hormone regulates postnatal expression of transient K+ channel isoforms in rat ventricle.

1. The ability of thyroid hormone to regulate the postnatal changes of the Ca2+-independent transient outward K+ current (It) was studied in rat ventricular myocytes. 2. In rat ventricle, It is very small at birth and then increases markedly between postnatal days 8 and 20. The time course of this increase in current density is similar to that of a significant rise in plasma thyroid hormone (T3) levels. 3. During early development, the density of expression of It can be altered by changes in thyroid hormone levels. Eight days after birth the density of It measured at +50 mV in control animals is 2.2 +/- 0.4 pA pF(-1). This value is about 3-fold larger (6.5 +/- 0.8 pA pF(-1)) in myocytes from age-matched hyperthyroid animals. When the plasma T3 level in newborn rats is not allowed to increase, or is decreased by making animals hypothyroid, this age-dependent increase in It fails to occur. 4. Using RNase protection assays, Kv4.2 and Kv4.3 mRNA levels were measured in ventricular tissues obtained from age-matched 8-day-old control and hyperthyroid rats. In hyperthyroid animals, where an approximately 3-fold increase in It was identified, increases in the mRNA levels for Kv4.2 and Kv4.3 were 1.6-fold and 2.6-fold, respectively. 5. These results show that thyroid hormone can regulate the development of It in rat ventricle. Direct measurements of It density and mRNA levels as a function of development and thyroid hormone levels also strongly suggest that the Kv4.2 and Kv4.3 channels are essential components of It in rat ventricular cells.

Aging↗
PubMed1996

Intramolecular disulfide bonds between conserved cysteines in wheat gliadins control their deposition into protein bodies.

Following synthesis, wheat gliadin storage proteins are deposited into protein bodies inside the endomembrane system in a way that enables not only their efficient accumulation and dehydration during seed maturation, but also their rapid rehydration and degradation during germination. In the present report, we studied the mechanism of gliadin deposition and whether it was controlled by the conformation of these proteins. Although gliadins are generally known to be insoluble in aqueous solutions, sucrose gradient analysis showed that a considerable amount of these proteins appeared as relatively soluble monomers in developing grains. In vitro reduction of the intramolecular disulfide bonds that are present in natural monomeric gliadins caused their precipitation into insoluble aggregates. In addition, pulse-chase experiments in the absence or presence of reducing agents showed that formation of intramolecular disulfide bonds also played a major role in folding and deposition of the gliadins in vivo. Our results imply that following sequestration into the endoplasmic reticulum, the gliadins fold into relatively soluble monomers, which are incompetent for rapid aggregation and gradually assemble into protein bodies. This pattern of deposition apparently depends on the conformation of the gliadins, which is stabilized by intramolecular disulfide bonds formed between the conserved cysteines. The contribution of this study to the understanding of the evolution and function of gliadins is discussed.

Amino Acid Sequence↗
PubMed1996

Mediation by nitric oxide of the indirect effects of adenosine on calcium current in rabbit heart pacemaker cells.

1. Adenosine (ADO) is a potent negative chronotropic agent in the mammalian myocardium. We have used single myocytes from rabbit sino-atrial node (SAN) to examine whether nitric oxide (NO) is a significant mediator of the effects of ADO on the pacemaker activity, or the underlying Ca2+ and K+ currents. 2. SAN pacemaker cells were isolated from rabbit hearts by enzymatic dispersion, and Ca2+ and K+ currents were recorded by the nystatin-perforated patch voltage clamp method. ADO was applied in the presence of the beta-adrenoceptor agonist, isopremaline (Iso) to mimic the adrenergic tone which the SAN is subjected to in vivo. 3. Control experiments confirmed that isolated SAN cells responded to ADO (10-100 microM) with the expected (i) small increase in background inwardly rectifying K+ current, IK-ADOi and (ii) pronounced decrease in L-type Ca2+ current, ICa-L. These effects were mimicked by a selective A1 purinoceptor agonist, N6-cyclopentyladenosine (CPA, 10 microM); and were inhibited following bath application of the antagonist, DPCPX (10 microM), which selectively blocks A1 purinoceptors. DMPX (10 microM), a blocker of A2 purinoceptor, had no effect on the actions of ADO. 4. A nitric oxide synthase inhibitor, L-NMMA (100 microM), abolished the inhibitory effect of ADO on ICa-L but did not alter activation of IK-ADO. After L-NMMA washoff, it was possible to obtain the normal response (inhibition) of ICa-L to ADO in the same cell. 5. To evaluate whether the observed effect of nitric oxide (NO) on ICa-L was mediated by an increase in guanylyl cyclase (GC) activity and cyclic GMP formation, the guanylyl cyclase inhibitor, LY 83583 (40 microM) was applied prior to ADO. Under these conditions, the inhibitory effect of ADO on ICa-L was abolished, but the activation of IK-ADO was still observed. 6. In combination, these findings strongly suggest that in mammalian primary pacemaker tissue which is under adrenergic tone, the effects of ADO on ICa-L are mediated by NO.

Action Potentials↗
PubMed1995

Thyroid status and diabetes modulate regional differences in potassium currents in rat ventricle.

1. The rate dependence and recovery kinetics of the Ca(2+)-independent transient (I(t)) and steady-state or 'pedestal' (Iss) outward potassium (K+) currents were studied in single myocytes isolated from epicardial and endocardial regions of rat left ventricles. The whole-cell, suction microelectrode method was used to measure baseline (fully reactivated) I(t), as well as its rate-dependent attenuation. Results from a group of control animals were compared with data from three other groups having an experimentally altered hormonal status. 2. I(t) was significantly smaller in endocardial cells than in epicardial cells, in part due to a very large difference in the recovery kinetics of this current in endocardial cells. This was reflected in a pronounced rate-dependent prolongation of endocardial action potentials. In contrast, the non-inactivating 'pedestal' current, Iss, was very similar in magnitude and showed comparable rate dependence in cells from both epicardium and endocardium. 3. Changing the thyroid status had selective, differential actions on the amplitude and rate dependence of It in epicardial and endocardial cells. Under hypothyroid conditions there was a more pronounced reduction of baseline I(t) in epicardial than in endocardial cells. Moreover, a slowing of the recovery kinetics in epicardial cells resulted in an enhanced attenuation of this current at high rates. Changing thyroid status had no effect on the magnitude or rate dependence of Iss in cells from either region of the left ventricle. 4. Following establishment of hyperthyroid conditions, there was no significant change in I(t) magnitude at baseline. However, when compared with control data, the recovery of I(t) was considerably faster in endocardial cells, and marginally faster in epicardial cells. 5. Streptozotocin-induced diabetic conditions resulted in a much greater attenuation of I(t) in epicardial cells than in endocardial cells. Epicardial action potentials in these conditions showed prominent rate-dependent prolongation. Iss was reduced to a similar extent in cells from these two regions. 6. Our findings demonstrate that altered hormonal status can selectively change the amplitude and kinetics of It in the epi- and endocardium of rat left ventricle. These changes can reduce the epicardial-endocardial gradients in the magnitude and recovery kinetics of It and hence diminish the intrinsic differences in both action potential duration and refractoriness.

Action Potentials↗
PubMed1995

A cellular mechanism for nitric oxide-mediated cholinergic control of mammalian heart rate.

The biochemical signaling pathways involved in nitric oxide (NO)-mediated cholinergic inhibition of L-type Ca2+ current (ICa[L]) were investigated in isolated primary pacemaker cells from the rabbit sinoatrial node (SAN) using the nystatin-perforated whole-cell voltage clamp technique. Carbamylcholine (CCh; 1 microM), a stable analogue of acetylcholine, significantly inhibited ICa(L) after it had been augmented by isoproterenol (ISO; 1 microM). CCh also activated an outward K+ current, IK(ACh). Both of these effects of CCh were blocked completely by atropine. Preincubation of the SAN cells with L-nitro-arginine methyl ester (L-NAME; 0.2-1 mM), which inhibits NO synthase (NOS), abolished the CCh-induced attenuation of ICa(L) but had no effect on IK(ACh). Coincubation of cells with both L-NAME and the endogenous substrate of NOS, L-arginine (1 nM), restored the CCh-induced attenuation of ICa(L), indicating that L-NAME did not directly interfere with the muscarinic action of CCh on ICa(L). In the presence of ISO the CCh-induced inhibition of ICa(L) could be mimicked by the NO donor 3-morpholino-sydnonimine (SIN-1; 0.1 mM). SIN-1 had no effect on its own or after a maximal effect of CCh had developed, indicating that it does not inhibit ICa(L) directly. SIN-1 failed to activate IK(ACh), demonstrating that it did not activate muscarinic receptors. Both CCh and NO are known to activate guanylyl cyclase and elevate intracellular cGMP. External application of methylene blue (10 microM), which interferes with the ability of NO to activate guanylyl cyclase, blocked the CCh-induced attenuation of ICa(L). However, it also blocked the activation of IK(ACh), suggesting an additional effect on muscarinic receptors or G proteins. To address this, a separate series of experiments was performed using conventional whole-cell recordings with methylene blue in the pipette. Under these conditions, the CCh-induced attenuation of ICa(L) was blocked, but the activation of IK(ACh) was still observed. Methylene blue also blocked the SIN-1-induced decrease in ICa(L). 6-anilino-5,8-quinolinedione (LY83583; 30 microM), an agent known to decrease both basal and CCh-stimulated cGMP levels, prevented the inhibitory effects of both CCh and SIN-1 on ICa(L), but had no effect on the activation of IK(ACh) by CCh. In combination, these results show that CCh- and NO-induced inhibition of ICa(L) is mediated by cGMP.(ABSTRACT TRUNCATED AT 400 WORDS)

1-Methyl-3-isobutylxanthine↗
PubMed1995

Purification, characterization, and intracellular localization of glycosylated protein disulfide isomerase from wheat grains.

Wheat (Triticum aestivum) storage proteins fold and assemble into complexes that are linked by intra- and intermolecular disulfide bonds, but it is not yet clear whether these processes are spontaneous or require the assistance of endoplasmic reticulum (ER)-resident enzymes and molecular chaperones. Aiming to unravel these processes, we have purified and characterized the enzyme protein disulfide isomerase (PDI) from wheat endosperm, as well as studied its developmental expression and intracellular localization. This ER-resident enzyme was previously shown to be involved in the formation of disulfide bonds in secretory proteins. Wheat PDI appears as a 60-kD glycoprotein and is among the most abundant proteins within the ER of developing grains. PDI is notably upregulated in developing endosperm in comparison to embryos, leaves, and roots. In addition, the increase in PDI expression in grains appears at relatively early stages of development, preceding the onset of storage protein accumulation by several days. Subcellular localization analysis and immunogold labeling of electron micrographs showed that PDI is not only present in the lumen of the ER but is also co-localized with the storage proteins in the dense protein bodies. These observations are consistent with the hypothesis that PDI is involved in the assembly of wheat storage proteins within the ER.

Amino Acid Sequence↗
PubMed1995

Thyroid status and potassium currents in rat ventricular myocytes.

The size and rate dependence of the transient (Ito) and steady-state (Iss) outward potassium currents were investigated in isolated rat ventricular myocytes obtained from euthyroid, hyperthyroid, and hypothyroid rats, using the whole cell, suction electrode voltage-clamp method. Under hypothyroid conditions Ito was reduced in size, with no significant change in Iss. In hypothyroid cells, the rate dependence of both currents was greatly enhanced, resulting in a much larger attenuation with increasing stimulation rates. A significant slowing of the recovery kinetics of Ito was observed. These effects of hypothyroidism were reversed by physiological triiodothyronine (T3) replacement. These current changes were reflected in an altered rate dependence of the action potential configuration in hypothyroid myocytes. Under hyperthyroid conditions no significant changes were observed in the amplitude or time course of recovery of Ito. Iss amplitude was increased, but no changes were found in its rate dependence. These results are discussed in terms of hormonal, long-term modulation of potassium currents, and in terms of cardiac pathology under conditions of altered thyroid status.

Animals↗
PubMed1994

An obligatory role for nitric oxide in autonomic control of mammalian heart rate.

Cholinergic modulation of heart rate in isolated spontaneously beating single cells from the rabbit sino-atrial node was investigated by measuring transmembrane ionic currents using the nystatin-perforated patch whole-cell voltage-clamp technique. Carbamylcholine (CCh), a stable analogue of acetylcholine (ACh), significantly inhibited L-type calcium currents (Ica(L) which had been augmented by beta-adrenergic stimulation. In addition, CCh activated a potassium outward current (IK(ACh)). Both effects were blocked by atropine. The possible involvement of nitric oxide (NO) in these responses was evaluated by inhibiting NO synthesis. In the presence of NG-monomethyl-L-arginine (L-NMMA, 100 microM) or nitro-L-arginine methyl ester (L-NAME, 1 mM), two specific inhibitors of nitric oxide synthase (NOS), CCh no longer inhibited ICa(L). IK(ACh) could still be activated. Co-incubation of cells in L-NAME or in L-NMMA with arginine (the endogenous substrate of NOS) restored the CCh-induced attenuation of ICa(L), indicating that L-NAME or L-NMMA did not interfere directly with the muscarinic action of CCh on ICa(L). Effects of the NO-releasing agent molsidomine (SIN-1) on CCh-induced changes in ICa(L) were also investigated. After ICa(L) had been augmented by beta-adrenergic stimulation, SIN-1 (0.1 mM) inhibited ICa(L); however, SIN-1 had no further inhibitory effect after a maximal CCh concentration had been applied. These findings suggest that NO generation is an obligatory process in cholinergic inhibition of ICa(L) in mammalian cardiac pacemaker tissue.

Acetylcholine↗
PubMed1994

Physiological changes induced in cardiac myocytes by cytotoxic lymphocytes: an autoimmune model.

BACKGROUND: cytotoxic lymphocytes are important in the pathogenesis of several disease states, yet, the pathophysiology of lymphocyte-myocyte interaction is not well known. METHODS AND RESULTS: We have developed a model for the in vitro evaluation of autoimmune cytotoxic myocardial damage. Cardiac myocytes were repeatedly injected to adult autologous rats. Following 3 months, histological evidence of myocarditis was seen in 20% of the hearts. Cultured myocytes obtained from newborn rats were exposed to lymphocytes isolated from the immunized animals. Cytotoxic activity was measured using crystal violet staining test. The percentage of killing was increased as the ratio of lymphocytes/myocytes was increased. Verapamil did not block this cytotoxic effect. No killing was seen when myocytes were exposed to non-sensitized lymphocytes. Physiological changes induced in myocytes by cytotoxic lymphocytes were studied. Cell wall motion was measured by an optical method and action potentials with intracellular microelectrodes. Physiological changes observed in myocytes following exposure to cytotoxic lymphocytes included: Impaired relaxation with prolonged contractions, oscillations and prolongation of the plateau of the action potential. Cellular contraction was prolonged up to 4 s before total arrest of spontaneous activity. Verapamil but not tetrodotoxin restored action potentials and contractions to normal. Supernatant collected from cultures of myocytes and lymphocytes had the same effect on myocytes contractility as observed following exposure of myocytes to cytotoxic lymphocytes. CONCLUSIONS: This supports our hypothesis that these physiological alterations observed in myocytes are mediated by a soluble factor secreted by cytotoxic lymphocytes.

Action Potentials↗
PubMed1994

Short-term diabetes alters K+ currents in rat ventricular myocytes.

The electrophysiological properties of single ventricular myocytes from control rats and from rats made diabetic by streptozotocin (STZ) injection (100 mg/kg body weight) have been investigated using whole-cell voltage-clamp measurements. Our major goal was to define the effects of diabetes on rate-dependent changes in action potential duration and the underlying outward K+ currents. As early as 4 to 6 days after STZ treatment, significant elevation of plasma glucose levels occurs, and the action potential duration increases. In both control and diabetic rats, when the stimulation rate is increased, the action potential is prolonged, but this lengthening is considerably more pronounced in myocytes from diabetic rats. In ventricular myocytes from diabetic rats, the Ca(2+)-independent transient outward K+ current (I(t)) is reduced in amplitude, and its reactivation kinetics are slowed. These changes result in a smaller I(t) at physiological heart rates. The steady-state outward K+ current (IK) also exhibits rate-dependent attenuation, and this phenomenon is more pronounced in cells from diabetic rats. These STZ-induced changes in I(t) and IK also develop when a lower dose (55 mg/kg) of STZ is used and measurements are made after 7 weeks of treatment. These electrophysiological effects are not related to the hypothyroid conditions that accompany the diabetic state, since they cannot be reversed by replacement of the hormone L-triiodothyronine to physiological levels. Direct effects of STZ could be ruled out, since preceding the STZ injection with a bolus injection of 3-O-methylglucose, which prevents development of hyperglycemia, prevents the electrophysiological changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1994

Ultrasound controlled operative hysteroscopy.

BACKGROUND: Uterine perforation is one of the risks of operative hysteroscopy. Although usually performed alone, laparoscopy has been recommended to aid the surgeon in preventing uterine perforation at the time of operative hysteroscopy. STUDY DESIGN: Since women suffering from infertility or habitual abortion with known or suspected intrauterine pathologic factors are at low risk for secondary pelvic abnormalities, we have been using ultrasound for control during operative hysteroscopy in these women. One hundred twenty-eight women underwent ultrasound-guided operative hysteroscopy. RESULTS: There were no complications, such as uterine perforation, during or after any of the procedures. CONCLUSIONS: Women with known intrauterine pathologic factors should be offered operative hysteroscopy controlled by ultrasound, avoiding the use of unnecessary laparoscopy.

Female↗
PubMed1993

Thyroid hormone induces earlier onset of auditory function in neonatal rats.

The effect of thyroid hormone injection on the development of auditory function in neonatal rats was evaluated using auditory nerve-brainstem evoked responses (ABR). The hormone induced earlier onset of auditory function. In order to differentiate between conductive and sensorineural factors, both air-conducted (AC) and bone-conducted (BC) ABR responses were recorded. Neonatal rats were injected with thyroxine (T4), or with saline (control animals), from day of birth (post-natal day-PND-0), daily, until PND 9. AC- and BC-ABRs were recorded from PND 6 up to PND 20. It was found that both AC- and BC-ABR thresholds were lower in the T4-injected rats up to PND 15, after which no difference was found between the two groups. This indicated earlier maturity of both conductive (external and middle ears) and sensorineural (inner ear) factors and is probably due to the earlier appearance in the blood of higher T4 levels, following injection, than that occurring naturally during the neonatal period in these animals.

Animals↗
PubMed1993

Alpha-adrenergic modulation of transient outward current in hyperthyroid rabbit myocytes.

The alpha 1-adrenergic modulation of the transient outward potassium current (I(t)) was studied in single cardiac myocytes obtained from normal (euthyroid) and hyperthyroid rabbits. Rabbits were made hyperthyroid by four or five daily intraperitoneal injections of 0.4 mg/kg body wt thyroxine. Currents were recorded using the whole cell, suction-electrode, voltage-clamp method. It was found that the alpha-adrenergic agonist methoxamine attenuates I(t) in rabbit ventricular cells, as reported earlier for atrial cells. This attenuation is significantly reduced in the hyperthyroid state. For example, 0.2 mM reduces I(t) magnitude (at +20 mV) by close to 40% in euthyroid cells and by only 20% in the hyperthyroid cells. Half-maximal effective concentration values (extrapolated) are close to 0.4 mM in normal and 1 mM in hyperthyroid cells. Preliminary results show similar effects in atrial cells as well. These results may be related to a decrease in the density of membrane alpha-adrenergic receptors in hyperthyroid conditions, or to the induction of a new class of I(t) channels that is less sensitive to alpha-agonists.

Animals↗
PubMed1993

Thyroxine effects on temperature dependence of ionic currents in single rabbit cardiac myocytes.

Macroscopic whole cell currents were measured from single rabbit cardiac myocytes, using the suction electrode voltage-clamp technique, under euthyroid, hyperthyroid, and hypothyroid conditions. In ventricular myocytes, the temperature dependence of the transient outward current (I(t)) was greatly reduced in hyperthyroid conditions, with Q10 values (between 22 and 32 degrees C) reduced from normal values of 6.14 +/- 0.93 (SE, n = 8) to 2.14 +/- 0.14 (n = 6). In contrast, two of the other major currents in these cells were relatively unaffected. Under hyperthyroid conditions, there was very little change in the amplitudes or temperature dependence of L-type calcium currents and of steady-state currents, which reflect mainly the inwardly rectifying potassium current. In atrial cells no changes in the temperature dependence of I(t) were observed, with virtually identical Q10 values (close to 4) in eu- and hyperthyroid conditions. Under hypothyroid conditions, there was no change in the temperature dependence of I(t) in either ventricular or atrial cells. We conclude that the regulation of I(t) in ventricular cells is unique, rendering it extremely sensitive to temperature changes and to elevations in thyroxine levels. These results are discussed in the context of long-term regulation of ionic channels.

Action Potentials↗
PubMed1992

Retrograde seeding of endometrial carcinoma during hysteroscopy.

Fractional dilatation and curettage remain the most reliable methods in the diagnosis of endometrial carcinoma in the symptomatic patient. In the past few years hysteroscopy has become a helpful method, improving the specificity of the diagnosis of this pathology. We report a case of clinical stage IA grade 2 endometrial adenocarcinoma diagnosed by hysteroscopy and endometrial biopsy. Surgical staging revealed positive cytology. We suggest that irrigation of the endometrial cavity during the hysteroscopic procedure with saline may disseminate the disease to the abdominal cavity and may change the prognosis and the course of treatment.

Adenocarcinoma↗
PubMed1992

Role of an inwardly rectifying potassium current in rabbit ventricular action potential.

1. Whole-cell voltage-clamp measurements were made of the time- and voltage-dependent properties of the inwardly rectifying background potassium current IK1, in single myocytes from rabbit ventricle. The main goal of these experiments was to define the role of IK1 in the plateau and repolarization phases of the action potential (AP). 2. Action potentials from single ventricular myocytes were used as the command signals for voltage-clamp measurements. In these 'action potential voltage-clamp' experiments, IK1 was isolated from other membrane currents by taking the difference between control currents and currents in K(+)-free bathing solution. The results show that IK1 is small during the plateau, but then rapidly increases during repolarization and declines in early diastole. 3. Evidence of an important functional role for IK1 in AP repolarization was obtained by comparing the magnitude of IK1 and the rate of change of membrane potential (dVm/dt) in the same cell during the AP. The time courses of IK1 and dVm/dt during the AP were closely correlated, indicating that IK1 was the principal current responsible for final repolarization. 4. Rectangular voltage-clamp steps were used to study time- and voltage-dependent changes in IK1 at membrane potentials corresponding to the repolarization phase of the AP. 'Slow' relaxations or tail currents, lasting 100-300 ms, were consistently recorded when the cell was repolarized to potentials in the range -30 to -70 mV, following depolarizations between +10 and -10 mV. 5. The close correlation between the magnitude of the steady-state IK1 (in an external K+ concentration of 5.4 mM), which was outward for membrane potentials in the range -30 to -70 mV, and the magnitude of the tail currents, suggests that they resulted from a slow increase, or reactivation, of IK1. 6. The component of the slow tails due to reactivation of IK1 can be separated from a previously described component due to Na(+)-Ca2+ exchange since the IK1 component: (i) does not depend on the presence of the calcium current, ICa; (ii) can be recorded when internal EGTA (5 mM) suppresses large changes in [Ca2+]i; (iii) does not depend on the Na+ electrochemical gradient; (iv) is abolished in K(+)-free external solution; and (v) is not present in rabbit atrial myocytes, in which IK1 is very small. 7. The time- and voltage-dependent properties of IK1 revealed by these tail current experiments suggest that the measured magnitude of IK1 will be dependent on the voltage-clamp protocol.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1992

Hyperthyroidism selectively modified a transient potassium current in rabbit ventricular and atrial myocytes.

1. Transient outward potassium currents (I(t)) were compared in single cardiac myocytes obtained from normal and hyperthyroid rabbits. Currents were recorded using the suction electrode whole-cell voltage clamp technique. 2. In ventricular myocytes from hyperthyroid animals (at 22 degrees C and a stimulation rate of 0.2 Hz), I(t) was 4- to 5-fold larger than in normal myocytes, in a potential range of -20 to +60 mV. As in normal myocytes, I(t) in hyperthyroid myocytes was calcium insensitive, and was more than 90% suppressed by 2 mM 4-aminopyridine. 3. The increase in I(t) was observed over a wide range of stimulation rates, even at rates sufficiently slow to enable complete reactivation of the I(t) channels. However, there was a major change in the rate dependence of I(t) in hyperthyroid myocytes, with significant I(t) current still present at rates (e.g. 1-2 Hz) at which it is normally completely suppressed. 4. The augmentation of I(t) in the hyperthyroid myocytes could not be accounted for by changes in the voltage dependence or the kinetics of channel activation or inactivation. There was no change in the reversal potential of I(t), implying no change in the selectivity of the channel. 5. Single-channel activity was recorded using the cell-attached mode of recording. In myocytes from hyperthyroid rabbit we observed the following: (a) active patches (often containing two channels) were obtained more frequently in comparison to control; (b) the unitary conductance of the channel was the same; (c) single-channel openings persisted at high stimulation rates. 6. In contrast to hyperthyroid ventricular cells, I(t) in atrial cells from the same hearts was not substantially changed. 7. The rate dependence of I(t) in atrial cells was also unaffected by hyperthyroidism, in contrast to the large changes observed in ventricular cells. Thus, in atrial cells from hyperthyroid hearts the current was totally suppressed at rates of 1-2 Hz, as in euthyroid conditions. 8. Single-channel recordings in the cell-attached mode showed a unitary conductance similar to that found in normal atrial cells. Channel activity was suppressed at 2 Hz, in contrast to hyperthyroid ventricular cells. 9. In conclusion, I(t) is drastically changed in hyperthyroid rabbit ventricle cells. The changes are in the magnitude of the macroscopic current and its rate dependence. Since the unitary conductance is unchanged (and the peak open probabilities are normally high at positive membrane potential(s) the number of active channels in the membrane must be increased. In atrial cells from the same hyperthyroid hearts no changes are apparent.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗