Effects of extracellular potassium on ventricular automaticity and evidence for a pacemaker current in mammalian ventricular myocardium.

Katzung, Bertram G.; Morgenstern, J

doi:10.1161/01.res.40.1.105

Cited by 129 publications

(39 citation statements)

References 27 publications

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“…The open channel I-V relation of I. is similar to that of IX1 whereas the slow kinetics of I, are rather more similar to those of I2x. A current resembling I., appears to be a general feature of adult ventricular myocardium (Beeler & Reuter, 1970;McGuigan, 1974;Katzung & Morgenstern, 1977;McDonald & Trautwein, 1978;Cleemann & Morad, 1979), and it has also been reported in frog atrial cells (Brown, Clark & Noble, 1976b Noble, 1966) which has also been reported for adult ventricular myocardium (Beeler & Reuter, 1970;McGuigan, 1974;Cleemann & Morad, 1979) and adult atrium (Noble, 1976). This current appears to be carried partly, although not exclusively, by potassium ions, since its equilibrium potential is changed by K. somewhat less than what is predicted for a potassium electrode (Fig.…”

Section: Determination Of Ibgsupporting

confidence: 57%

Analysis of subthreshold pace‐maker currents in chick embryonic heart cells.

Clay¹,

Shrier²

1981

The Journal of Physiology

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SUMMARY1. Small re-aggregates of cells dissociated from the ventricles of 7-day-old chick embryonic hearts beat spontaneously in low external potassium concentration (K0 = 1-3 mM) tissue culture medium. This activity was blocked by the addition of tetrodotoxin (TTX) or potassium ions to the external medium.2. A two-micro-electrode voltage-clamp technique was used to analyse the subthreshold currents responsible for the pace-maker depolarization.3. Voltage-clamp steps 6-10 see in duration revealed a time-dependent current having first order kinetics. Its membrane potential range of steady-state activation was -90 to -60 mV.4. The current kinetics were qualitatively similar to those of Hodgkin & Huxley (1952b) with a peak time constant of approximately 1 see at V =-75 mV. The kinetics were independent of K0.5. The time-dependent current was attributed to gated membrane channels. The fully activated current-voltage (I-V) relation of the channels was determined from the ratio of the amplitudes of the time-dependent currents during and after voltage-clamp steps following the procedure of Noble & Tsien (1968).6. The fully activated I-V relation displayed inward rectification with negative slope conductance at potentials more than 15 mV positive to its reversal potential.Changes of Ko shifted the I-V curve along the voltage axis like a potassium electrode.7. The time-independent (background) current was obtained by subtracting the gated channel current from the steady-state I-V curve. This current also rectified in the inward direction.8. The inwardly rectifying I-V relations were theoretically described by a channel having a row of ion-selective sites along which ions move in a single file (Hodgkin & Keynes, 1955), and a membrane-bound particle which blocked the channel in a voltage-dependent manner.9. The relationship ofthe voltage-clamp results to spontaneous activity is discussed and comparisons are made with measurements from whole embryonic heart and other cardiac tissues.

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Section: Determination Of Ibgsupporting

confidence: 57%

Analysis of subthreshold pace‐maker currents in chick embryonic heart cells.

Clay¹,

Shrier²

1981

The Journal of Physiology

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“…If the concentration of Cs used in our experiments was sufficient to block gkl, we are left with the possibility that the component i, of the outward current is the one involved in the action of salicylate. This is also in agreement with the results obtained by Cohen et al (1979b) (Katzung & Morgenstern, 1977;MacDonald & Trautwein, 1978). APD is also shortened by a direct reduction of the slow inward current (Paes de Carvalho, Hoffman & Paula Carvalho, 1969;Wit & Cranefield, 1975;Eick, Nawrath, McDonald & Trautwein, 1978 (Eick et al, 1978) would also explain the decreased contractility found in the muscle fibres treated with salicylate (Blood, 1977) and the relative inefficacy of calcium ions in antagonizing the effect in the plateau duration.…”

Section: Effects Of5-bromo Salicylate In Tyrode Solution Containingcasupporting

confidence: 93%

Electrophysiological Effects of the Salicylates on Isolated Atrial Muscle of the Rabbit

Neto

1982

British J Pharmacology

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1 Intracellular recordings were made from cells of the sinoatrial (S-A) node region and from atrial muscle fibres of rabbit hearts. The effects of sodium salicylate and 5-bromo salicylate on various parameters of the membrane action potential were studied.2 5-Bromo salicylate (30-100gaM) and sodium salicylate (300-500tiM) caused a dose-dependent decrease in the frequency of discharge of the SA node cells. Applications of atropine (2.6 AiM) with propranolol (3.3 liM) did not affect the negative chronotropic effect, whereas adrenaline (5 tLM) reversed it. 3 Depolarization and shortening of the action potential duration were found in atrial muscle fibres after the application of 5-bromo salicylate (60-100IM). The reduction of the action potential duration (APD) was not affected by atropine (2.6 ItM). 4 Higher concentrations of 5-bromo salicylate (>100 gM) also caused a dose-dependent reduction in the action potential amplitude (APA), in the overshoot (OS) of the action potential and in the maximum rate of rise of the action potential (V,,,,=). All these effects were completely reversed on washing. 5 Substitution of the NaCl of the bathing Tyrode solution by an equimolar concentration of Na isethionate did not affect the plateau depression induced by the salicylates in atrial muscle fibres.6 After increasing the K concentration to 27 mM in the presence of isoprenaline (1 PM), 'slow responses' were obtained upon stimulation. 5-Bromo salicylate (20-601AM) and sodium salicylate (100 pAM) decreased reversibly the amplitude and the rate of rise of the 'slow response'. 7 A four fold increase in Ca concentration of the standard Tyrode solution did not antagonize the plateau depression of atrial muscle fibres or the negative chronotropism induced by salicylates. 8 Addition of CsCl (10 mM) to the Tyrode solution did not affect the shortening of the APD induced by the salicylates in atrial muscle fibres. 9 When the K concentration in the Tyrode solution was increased from 2.7 mM to 5.4 mM, the effects of 5-bromo salicylate on the APA, OS and V,,,,, were potentiated. However, a significant reduction in the shortening of the APD produced by the salicylate was observed. 10

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“…Two types of automaticity have been shown in animal Purkinje fibers: one which occurs at membrane potentials of around -90 mV referred to as "normal automaticity" and the other that occurs at membrane potentials of -40 to -60 mV referred to as "abnormal automaticity" (19,31,32). In response to increasing rates and duration of overdrive pacing, normal automaticity may exhibit progressive postpacing cycle length lengthening, whereas abnormal automaticity usually appears nonsuppressible and may actually slightly increase in rate.…”

Section: Discussionmentioning

confidence: 99%

Effects of beta-adrenergic blockade on verapamil-responsive and verapamil-irresponsive sustained ventricular tachycardias.

Sung

Keung²,

Nguyen³

et al. 1988

J. Clin. Invest.

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IntroductionTo assess effects of el-adrenergic blockade on ventricular tachycardia (VT) of various mechanisms, electrophysiology studies were performed before and after intravenous infusion of propranolol (0.2 mg/kg) in 33 patients with chronic recurrent VT, who had previously been tested with intravenous verapamil (0.15 mg/kg followed by 0.005 mg/kg/min infusion). In the verapamil-irresponsive group, 10 patients (group IA) had VT that could be initiated by programmed ventricular extrastimulation and terminated by overdrive ventricular pacing, and 11 patients (group IB) had VT that could be provoked by isopro- (5) found that intravenous propranolol slowed the sinus rate but did not affect the VT rate and its inducibility. We and others (6-9), in contrast, observed that intravenous propranolol was effective in suppressing VT inducibility in patients in whom VT was provocable with intravenous infusion of isoproterenol. The disparity in responses to ,B-adrenergic blockade connotes that the occurrence of VT may be accounted for by different electrophysiologic mechanisms.Using the technique of programmed electrical stimulation along with pharmacologic testing with intravenous verapamil, we have previously separated three "presumptive" mechanisms of VT in human beings: reentry, catecholamine-sensitive automaticity, and triggered activity related to delayed afterdepolarizations (10). In the present study, we assessed effects of ,B-adrenergic blockade on these three forms ofVT. Our findings indicate that f3-adrenergic blockade is only specifically effective in suppressing VT suggestive of catecholamine-sensitive automaticity. MethodsPatients. Between July 1983 and July 1986, we studied 33 patients with clinically documented sustained VT that could be reproduced during the course of electrophysiologic evaluation. Sustained VT was defined as VT that lasted longer than 30 s. We excluded patients who were hemodynamically unstable and who had a prior history of congestive heart failure or who had an ejection fraction of < 40% as measured by radionuclide angiography (1 1). All 33 patients had had echocardiography and treadmill exercise testing using the standard Bruce protocol (12) before electrophysiology studies. Additionally, 24 patients had undergone cardiac catheterization with coronary angiography as clinically indicated. There were 22 men and 11 women ranging in ages from 18 to 66 (mean 42.5) yr (Tables I-III). 10 patients had arteriosclerotic heart disease with prior myocardial infarction of > 6 mo, 5 patients had idiopathic cardiomyopathy, and 18 patients had no clinical evidence of structural heart disease. All patients were clinically symptomatic with palpitations, dizziness, and/or syncope. Plasma concentrations ofcatecholamines. In patients with VT provocable with treadmill exercise testing, blood samples were drawn for measurements of plasma epinephrine and norepinephrine levels 1. Abbreviations used in this paper: VT, ventricular

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Effects of extracellular potassium on ventricular automaticity and evidence for a pacemaker current in mammalian ventricular myocardium.

Cited by 129 publications

References 27 publications

Analysis of subthreshold pace‐maker currents in chick embryonic heart cells.

Analysis of subthreshold pace‐maker currents in chick embryonic heart cells.

Electrophysiological Effects of the Salicylates on Isolated Atrial Muscle of the Rabbit

Effects of beta-adrenergic blockade on verapamil-responsive and verapamil-irresponsive sustained ventricular tachycardias.

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