Effects of Veratridine on the Action Potentials and Contractility of Right and Left Ventricles From Normo‐ and Hypertensive Rats

Nand, Vinita; Doggrell, Sheila A; Barnett, Carolyn W.

doi:10.1111/j.1440-1681.1997.tb02092.x

Cited by 10 publications

(10 citation statements)

References 12 publications

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“…We have previously described the method for recording ventricular contractility 4 . Five strips were prepared from the left ventricle free wall.…”

Section: Methodsmentioning

confidence: 99%

“…We have previously described the method for recording ventricular action potentials. 4 Strips representing approximately one-fifth of the left ventricle were pinned, endocardial-side uppermost, to the silicone polymer base of a recording chamber between two platinum stimulating electrodes. Strips were superfused at approximately 2 mL/min with Krebs'solution that had been vigorously bubbled with 5% CO2 in O2 before entering the recording chamber.…”

Section: Recording Of Action Potentials From Electrically Driven Ventmentioning

confidence: 99%

“…3 We have recently demonstrated that the effects of prolonging the opening of sodium channels with veratridine are reduced in the left ventricles of 22-but not 14-week-old spontaneously hypertensive rats (SHR). 4 This demonstrates that the response to prolonging the opening of sodium channels may be changed in persistent hypertension-associated hypertrophy. BDF 9148 is a novel synthetic compound that also prolongs the opening of cardiac tetrodotoxin-resistant sodium channels and is a positive inotrope under physiological conditions.…”

Section: Introductionmentioning

confidence: 96%

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Effects of BDF 9148 on the Action Potentials and Contractions of Left Ventricles From Normo‐ and Hypertensive Rats

Nand

Doggrell

1999

Clin Exp Pharma Physio

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1. The aim of the present study was to test the hypothesis that responses to BDF 9148, which prolongs the opening of sodium channels, are reduced in the spontaneously hypertensive rat (SHR) left ventricle in the presence of hypertrophy and failure. 2. We studied the effects of BDF 9148 on the action potentials and contractions of left ventricles from 5-week-old prehypertensive, 14-week-old hypertensive, 6- and 12-month-old hypertension-associated hypertrophy and 18-month-old hypertension-induced heart failure SHR and age-matched Wistar-Kyoto normotensive (WKY) rats. 3. Action potentials and left ventricular contractions did not alter in the early stages of hypertension (14-week-old SHR). The diastolic membrane potential did not change with hypertension-associated hypertrophy, but there was a reduction in amplitude and a prolongation of action potentials in the left ventricles of 6-18-month-old SHR. Cardiac stimulation responses and maximum contractions to 10(-6) mol/L isoprenaline were reduced at 6 months, whereas the maximum contractions to 10(-2) mol/L CaCl2 were only reduced in left ventricles of 18-month-old SHR. 4. At concentrations ranging from 10(-7) to 3 x 10(-6) mol/L, BDF 9148 increased the amplitude and prolonged the duration of action potentials and augmented the force in WKY rat left ventricles. The augmenting effects of BDF 9148 at 3 x 10(-6) mol/L were smaller than at 10(-6) mol/L, possibly because the high concentration of BDF 9148 was also blocking calcium channels. Similar effects were observed with BDF 9148 in the early stages of hypertension (14-week-old SHR). 5. In the presence of persistent hypertension-associated hypertrophy of the SHR left ventricle at > or = 6 months, the effects of BDF 9148 on action potentials and contractions were significantly reduced to a small extent. This impairment of the response to BDF 9148 may reflect the reduced contractility of the SHR left ventricle and/or it may indicate that the response to the opening of sodium channels is altered from 6 months of age. 6. In summary, most of the response of BDF 9148 is maintained in the presence of hypertrophy and failure. Thus, BDF 9148 may have some potential for the treatment of heart failure.

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“…We have previously described the method for recording ventricular contractility 4 . Five strips were prepared from the left ventricle free wall.…”

Section: Methodsmentioning

confidence: 99%

Section: Recording Of Action Potentials From Electrically Driven Ventmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

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Effects of BDF 9148 on the Action Potentials and Contractions of Left Ventricles From Normo‐ and Hypertensive Rats

Nand

Doggrell

1999

Clin Exp Pharma Physio

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“…On the molecular level, SERCA expression has been shown to be reduced by about 30% in human hypertrophic obstructive cardiomyopathy or aortic valve stenosis, whereas the expression of phospholamban and the NCX were unchanged (Schotten et al 1999). Spontaneously hypertensive rats develop a stable hypertension of about 190 mmHg by the age of 3 months (Mill et al 1998), and after 14 weeks the left ventricle is hypertrophied (Nand et al 1997). An increased contractility has been found as response to pressure overload at this age (Mill et al 1998) as well as reduced (Diaz et al 2004) or unchanged contractile function (Perez et al 1993).…”

Section: Post-rest Potentiation Of Contractionmentioning

confidence: 96%

Age and hypertrophy related changes in contractile post-rest behavior and action potential properties in isolated rat myocytes

Weisser-Thomas

Nguyen

Schuettel

et al. 2007

AGE

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"Physiological" aging as well as early and progressive cardiac hypertrophy may affect action potential (AP) pattern, contractile function, and Ca(2+) handling. We hypothesize that contractile function is disturbed in hypertrophy from early stages and is differently affected in aged myocardium. In vivo function, cardiomyocyte contractile behavior and APs were compared in Wistar-Kyoto (WIS) rats and spontaneously hypertensive rats (SHR) at different ages and degrees of hypertrophy (3-4, 9-11, 20-24 months). Post-rest (PR) behavior was used to investigate the relative contribution of the sarcoplasmic reticulum (SR) and the Na/Ca exchanger (NCX) to cytosolic Ca(2+) removal. APs were recorded by whole-cell current-clamp and sarcomere shortening by video microscopy. Cyclopiazonic acid was used to suppress Ca(2+) ATPase (SERCA) function. Heart weight/body weight ratio was increased in SHR versus WIS within all age groups. Myocyte steady state (SS) shortening amplitude was reduced in young SHR versus WIS. Aging led to a significant decay of SS contractile amplitude and relengthening velocity in WIS, but the PR potentiation was maintained. In contrast, aging in SHR led to a decrease of PR potentiation, while SS contraction and relengthening velocity increased. APD(50%) was always prolonged in SHR versus WIS. With aging, APD(50%) increased in both WIS and SHR, but was still shorter in WIS. However, in old WIS the late AP portion (APD(90%)) was prolonged. Ca(2+) handling and AP properties are disturbed progressively with aging and with increasing hypertrophy. Decreased amplitude of shortening and velocity of relengthening in aged WIS may be attributed to reduced SERCA function. In SHR, an increase in SR leak and shift towards transmembraneous Ca handling via NCX may be responsible for the changes in contractile function. A prolonged APD(90%) in aged WIS may be an adaptive mechanism to preserve basal contractility. Therefore, the effects on contractile parameters and AP are different in hypertrophy and aging.

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“…Low concentrations of the naturally occurring alkaloid veratridine prolong the action potential by preventing closure of the Na channel inactivation gate ( Honerjager, 1982 ) and have marked positive inotropic effects. Higher concentrations of veratridine, however, also open Na channels ( Honerjager, 1982 ) and can produce after‐depolarizations, ectopic beats and arrhythmias ( Doggrell et al ., 1995 ; Nand et al ., 1997 ). Veratridine also prolongs the opening of the neuronal Tetrodotoxin‐sensitive I channel to promote neurotransmitter release ( Honerjager, 1982 ).…”

Section: Introductionmentioning

confidence: 99%

Effects of BDF 9198 on action potentials and ionic currents from guinea‐pig isolated ventricular myocytes

Yuill¹,

Convery²,

Dooley

et al. 2000

British J Pharmacology

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1 BDF 9198 (a congener of DPI 201 ± 106 and BDF 9148) was found to be a positive inotrope on guinea-pig isolated ventricular muscle strips. The e ects of BDF 9198 on action potentials and ionic currents from guinea-pig isolated ventricular myocytes were studied using the whole cell patch clamp method. P50.001, n=7). At higher concentrations in the range tested, BDF 9198 also induced early and delayed and after-depolarizations. 3 Qualitative measurements of I Na with physiological [Na] o showed prolongation of the current by BDF 9198, and the appearance of transient oscillatory inward currents at high concentrations. 4 Quantitative recording conditions for I Na were established using low external [Na] and by making measurements at room temperature. The current ± voltage relation, activation parameters and timecourse of I Na were similar before and after a partial blocking dose of Tetrodotoxin (TTX, 1 mM), despite a 2 fold di erence in current amplitude. This suggests that voltage-clamp during¯ow of I Na was adequately maintained under our conditions. 5 Selective measurements of I Na at room temperature showed that BDF 9198 induced a concentration-dependent, sustained component of I Na (I Late ) and caused a slight left-ward shift in the current ± voltage relation for peak current. The drug-induced I Late showed a similar voltage dependence to peak current in the presence of BDF 9198. Both peak current and I Late were abolished by 30 mM TTX and were sensitive to external [Na]. 6 Inactivation of control I Na during a 200 ms test pulse to 730 mV followed a bi-exponential timecourse. In addition to inducing a sustained current component, BDF 9198 left the magnitude of the fast inactivation time-constant unchanged, but increased the magnitude of the slow inactivation time-constant. Additional experiments with a longer pulse (1 s) raised the possibility that in the presence of BDF 9198, I Na inactivation may be comprised of more than two phases. 7 No signi®cant e ects of 1610 76 M BDF 9198 were observed on the L-type calcium current, or delayed and inward rectifying potassium currents measured at 378C. 8 It is concluded that the prolongation of APD 50 by BDF 9198 resulted from selective modulation of I Na . Reduced current inactivation induced a persistent I Na , increasing the net depolarizing current during the action potential. This action of the drug indicates a potential for`QT prolongation' of the ECG. The observation of after-depolarizations suggests a potential for proarrhythmia at some drug concentrations.

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Effects of Veratridine on the Action Potentials and Contractility of Right and Left Ventricles From Normo‐ and Hypertensive Rats

Cited by 10 publications

References 12 publications

Effects of BDF 9148 on the Action Potentials and Contractions of Left Ventricles From Normo‐ and Hypertensive Rats

Effects of BDF 9148 on the Action Potentials and Contractions of Left Ventricles From Normo‐ and Hypertensive Rats

Age and hypertrophy related changes in contractile post-rest behavior and action potential properties in isolated rat myocytes

Effects of BDF 9198 on action potentials and ionic currents from guinea‐pig isolated ventricular myocytes

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