A slowly inactivating transient outward current in rat ventricular myocytes

Weis, T.; Berger, F; Borchard, U.

doi:10.1007/bf00374522

Cited by 7 publications

(13 citation statements)

References 4 publications

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“…The slope factors (K) were -19 mV (i to,s ) and -2 mV (i to,f ). These characteristics, the steeper slope of the i to,f inactivation curve and V 0.5 about 40 mV more positive than that for i to,s , agree with published results (Apkon and Nerbonne 1991;Weis et al 1993). These curve parameters were hardly affected by 10 or 30 µmol/l 17β-estradiol (Table 1).…”

Section: Resultssupporting

confidence: 80%

“…In this study the components were termed i to,f (τ inactivation = 34 ms) and i to,s (τ > 1 s). Both components not only differ in their kinetics of inactivation but also have different voltage dependencies of inactivation (Apkon and Nerbonne 1991;Weis et al 1993) and pharmacological sensitivities (Apkon and Nerbonne 1991;Lefevre et al 1991;Weis et al 1995). With respect to 17β-estradiol both components behaved similarly.…”

Section: Discussionmentioning

confidence: 82%

“…In rat ventricular myocytes two transient outward current components are obvious with respect to the time dependence of inactivation (Apkon and Nerbonne 1991;Lefevre et al 1991;Weis et al 1993). One component inactivated fast with a time constant (τ f ) of 34 ± 1.4 ms (n = 11, 50-60 mV, 24-26°C).…”

Section: Resultsmentioning

confidence: 99%

“…Voltage dependently inactivating (transient) outward current in rat ventricle is composed of two components with respect to the velocity of inactivation (Apkon and Nerbonne 1991;Lefevre et al 1991;Weis et al 1993). In this study the components were termed i to,f (τ inactivation = 34 ms) and i to,s (τ > 1 s).…”

Section: Discussionmentioning

confidence: 99%

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Effects of 17β-estradiol on action potentials and ionic currents in male rat ventricular myocytes

Berger

Borchard

Häfner

et al. 1997

Naunyn-Schmiedeberg's Arch Pharmacol

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This study describes electrophysiological effects of estrogens in isolated male rat ventricular myocytes. According to the literature these cells do not express the nuclear estrogen receptor. Action potentials or membrane currents were recorded in the whole-cell configuration with standard techniques. Action potential durations (APD) measured at a level of 0 mV (APD 0) and -70 mV (APD -70) were prolonged by 17beta-estradiol (0.5 Hz stimulation frequency, 24-26 degrees C). Threshold concentration was 1 micromol/l. At the highest concentration used (30 micromol/l) no saturation of the response was reached and APD 0 was 162% and APD -70 was 230% of the respective control. The resting potential remained unaffected in most cells. The prolongation induced by 17beta-estradiol developed fast and reached a steady state 10 min after start of hormone superfusion. Effects of estrogen were completely reversible during 10-15 min wash-out with hormone-free solution. The extent of prolongation (10 micromol/l 17beta-estradiol) was frequency dependent. Expressed as percentage of the respective control APD 0 (or APD -70) was 115% (188%) at 0.05 Hz, 118% (163%) at 0.5 Hz and 99% (129%) at 5 Hz stimulation frequency. The response was stereoselective, because 30 micromol/l 17alpha-estradiol did not prolong action potentials (APD 0: 101%, APD -70: 104% of the respective control, 0.5 Hz stimulation frequency). The endogenous estrogens estrone and estriol were less effective than 17beta-estradiol. With 30 micromol/l estrone (0.5 Hz stimulation frequency) APD 0 was 103% and ADP-70 148% of control and with 30 micromol/l estriol APD 0 was 135% and APD -70 137% of control. The prolongation of action potentials can be explained by inhibition of transient outward current which, in rat ventricle, is composed of fast (i[to,f]) and slowly (i[to,s]) inactivating components. At 30 micromol/l 17beta-estradiol i(to,f) was reduced to 50% and i(to,s) to 43% of their maximal amplitudes. The voltage sensor of i(to,f) or i(to,s) was hardly affected. Additionally, 17beta-estradiol decreased the calcium current (i[Ca,L]) to 76% (10 micromol/l) and 38% at 30 micromol/l. The inwardly rectifying potassium current (i[K1]) was reduced partly with 30 micromol/l 17beta-estradiol and its amplitude was 72% of control at -90 mV (inward current flow) and 65% at -40 mV (outward current flow). These results show that 17beta-estradiol is active in cardiac cells which do not express the nuclear estrogen receptor. The hormone exerts class III activity and reduces calcium inward current. These effects, however, occur in vitro with concentrations above the physiological level and therefore may be without significance in vivo.

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Section: Resultssupporting

confidence: 80%

Section: Discussionmentioning

confidence: 82%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Effects of 17β-estradiol on action potentials and ionic currents in male rat ventricular myocytes

Berger

Borchard

Häfner

et al. 1997

Naunyn-Schmiedeberg's Arch Pharmacol

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“…However, subsequent investigations demonstrated that besides the fast inactivating transient outward current (i to,f ) there exists a second prominent voltagedependently and slowly inactivating outward current i to,s at plateau potentials in rat ventricular myocytes (Apkon and Nerbonne 1991;Lefevre et al 1991;Weis et al 1993Weis et al , 1995. We therefore reinvestigated the effects of tedisamil and focussed our work on the differentiation of i to,f and i to,s and on the respective tedisamil-induced effects.…”

Section: Introductionmentioning

confidence: 99%

Different inhibition patterns of tedisamil for fast and slowly inactivating transient outward current in rat ventricular myocytes

Berger

Borchard

Häfner

et al. 1998

Naunyn-Schmiedeberg's Arch Pharmacol

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Tedisamil has been described as a selective inhibitor of a fast inactivating transient outward current (i(to,f)) in rat ventricular myocytes. Because recent reports demonstrated the existence of a second slowly inactivating transient component (i(to,s)) we investigated i(to,s) and differentiated the effects of tedisamil on both transient outward current components and their influence on action potential duration. Standard electrophysiological techniques were used for whole cell recordings at 24-26 degrees C from enzymatically isolated myocytes. Inhibition of i(to,f) by tedisamil was the result of an acceleration of inactivation at positive test potentials with a concentration for half-maximal inhibition (EC50) of 4-7 micromol/l, which is confirmatory to reports from other investigators. Our new results show that i(to,s) is more sensitive to tedisamil with an EC50 of 0.5 micromol/l. Furthermore the pattern of i(to,s) inhibition is different compared with i(to,f), because inactivation of i(to,s) is not accelerated by tedisamil. Instead the amplitude of the steady state inactivation curve of i(to,s) is attenuated which indicates a reduction of maximally available current. I(to,s) was evaluated by three different methods as time-dependently inactivating current (7.5 s test pulse duration), voltage-dependently inactivated current and tedisamil-sensitive current. All approaches yield similar inactivation curves. The potential for halfmaximal inactivation of i(to,s) lies about 35 mV more negative than that for i(to,f) and the slope factor (K = -23 mV) is different to that of i(to,f) (K = -3 mV). Effectiveness of tedisamil-induced modulation of i(to,f) and i(to,s) on action potential repolarization was tested. Action potentials stimulated at 0.5 Hz were not prolonged by 1 micromol/l tedisamil (dominant i(to,s) block) at a repolarization level of 0 mV but prolonged to about 120% of control at -70 mV. This indicates that i(to,f) was sufficient to guarantee a regular early repolarization whereas decrease of i(to,s) delayed the final repolarization. In conclusion, the observation that tedisamil inhibits i(to,f) and i(to,s) differently supports the hypothesis that the two i(to)-components are related to two different channel populations expressed in rat ventricular myocytes.

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A Mathematical Model of Action Potential Heterogeneity in Adult Rat Left Ventricular Myocytes

Pandit

Clark

Giles

et al. 2001

Biophysical Journal

267

367

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Mathematical models were developed to reconstruct the action potentials (AP) recorded in epicardial and endocardial myocytes isolated from the adult rat left ventricle. The main goal was to obtain additional insight into the ionic mechanisms responsible for the transmural AP heterogeneity. The simulation results support the hypothesis that the smaller density and the slower reactivation kinetics of the Ca(2+)-independent transient outward K(+) current (I(t)) in the endocardial myocytes can account for the longer action potential duration (APD), and more prominent rate dependence in that cell type. The larger density of the Na(+) current (I(Na)) in the endocardial myocytes results in a faster upstroke (dV/dt(max)). This, in addition to the smaller magnitude of I(t), is responsible for the larger peak overshoot of the simulated endocardial AP. The prolonged APD in the endocardial cell also leads to an enhanced amplitude of the sustained K(+) current (I(ss)), and a larger influx of Ca(2+) ions via the L-type Ca(2+) current (I(CaL)). The latter results in an increased sarcoplasmic reticulum (SR) load, which is mainly responsible for the higher peak systolic value of the Ca(2+) transient [Ca(2+)](i), and the resultant increase in the Na(+)-Ca(2+) exchanger (I(NaCa)) activity, associated with the simulated endocardial AP. In combination, these calculations provide novel, quantitative insights into the repolarization process and its naturally occurring transmural variations in the rat left ventricle.

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A slowly inactivating transient outward current in rat ventricular myocytes

Cited by 7 publications

References 4 publications

Effects of 17β-estradiol on action potentials and ionic currents in male rat ventricular myocytes

Effects of 17β-estradiol on action potentials and ionic currents in male rat ventricular myocytes

Different inhibition patterns of tedisamil for fast and slowly inactivating transient outward current in rat ventricular myocytes

A Mathematical Model of Action Potential Heterogeneity in Adult Rat Left Ventricular Myocytes

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