Electrophysiological effects of various ceveratrum alkaloids on single nerve axons

Honerjäger, P

doi:10.1007/bf00506631

Cited by 23 publications

(9 citation statements)

References 23 publications

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“…That an increase in ah, increases I,, is supported by the fact that low [K], increases ah, (Ellis 1977;Deitmer &Ellis 1978) andI,, (Goto et al 1977). Also, veratridine increases the Na influx (Honerjager 1973) and increases aha (Brill & Wasserstrom 1986) and I,, (Horackova & Vassort 1974;Marban & Tsien 1982), in agreement with the present results.…”

Section: Role Of Sodium In Regulation Of Intracellular Calciumsupporting

confidence: 93%

Effects of Strophanthidin on the Slow Inward Current in Guinea‐pig Isolated Ventricular Myocytes

Yang

Vassalle

1990

Clin Exp Pharma Physio

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1. The effect of strophanthidin on the slow inward current (Isi) and on contractile force were studied in guinea-pig isolated ventricular myocytes and intact papillary muscles, respectively. In myocytes, both low (10 nmol/L) and high (1-10 mumols/L) concentrations had small or no effects in either direction on Isi whereas norepinephrine (10-100 nmol/L) increased it. To determine whether the same results are obtained after decreasing or increasing intracellular calcium or sodium, the same concentrations of strophanthidin were tested in different procedures that are known to (i) increase [Ca]i and decrease [Na]i (high [Ca]o, 3.6-5.4 mmol/L; low [Na]o, 112 mmol/L; (ii) decrease [Ca]i and increase [Na]i (low [Ca]o, 0.45-1 mmol/L; Sr, 1 mmol/L; (iii) decrease [Ca]i and [Na]i (Cd, 0.1-0.2 mmol/L); and (iv) increase [Ca]i and [Na]i (veratridine, 0.2 mumol/L). High [Ca]o and veratridine increased whereas low [Ca]o and Cd decreased Isi. In contrast, during these various procedures, strophanthidin had small and inconsistent effects at a low or high concentration. In intact papillary muscles, low strophanthidin decreased whereas high strophanthidin increased contractile force. It is concluded that strophanthidin has little direct or indirect effect on Isi and that the decrease in force by low and increase in force by high concentrations in intact muscle are probably related to demonstrated decrease and increase, respectively, in intracellular sodium activity.

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Section: Role Of Sodium In Regulation Of Intracellular Calciumsupporting

confidence: 93%

Effects of Strophanthidin on the Slow Inward Current in Guinea‐pig Isolated Ventricular Myocytes

Yang

Vassalle

1990

Clin Exp Pharma Physio

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“…that veratridine and other ceveratrum alkaloids interact with tetrodotoxin-sensitive fast Na channels (Ulbricht, 1969;Honerjager, 1973). Under their influence, a small fraction of Na channels activate very slowly (r 5 sec) and fail to inactivate with maintained depolarization.…”

Section: Facilitatory Effects Of Action Potentialsmentioning

confidence: 99%

“…To explore the possible involvement of intracellular Na in regulating the slow inward current, we tried to increase Nai without interfering with the Na pump, through the use of veratridine (Fig. 5) that veratridine and other ceveratrum alkaloids interact with tetrodotoxin-sensitive fast Na channels (Ulbricht, 1969;Honerjager, 1973). Under their influence, a small fraction of Na channels activate very slowly (r 5 sec) and fail to inactivate with maintained depolarization.…”

Section: Facilitatory Effects Of Action Potentialsmentioning

confidence: 99%

Enhancement of calcium current during digitalis inotrophy in mammalian heart: positive feed‐back regulation by intracellular calcium?

Marbán

Tsien

1982

The Journal of Physiology

214

102

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SUMMARY1. Effects of digitalis compounds on slow inward Ca current Isi) and contractile force were examined in ferret ventricular muscle (single sucrose-gap voltage clamp) and calf Purkinje fibres (two micro-electrode voltage clamp).2. In ventricular muscle, ouabain increased I8i and inward current tails associated with Ii conductance. The enhancement of Isi followed a time course similar to the development of the positive inotropic effect, and it could be observed in the absence of aftercontractions or other signs of toxicity.3. The response of myocardial Ii and twitch force to ouabain depended strongly on a previous history of driven action potentials.4. Veratridine, a toxin that promotes Na entry through tetrodotoxin-sensitive channels, also increased ISi and twitch force in driven ventricular muscle preparations.5. The effects ofouabain, action potential stimulation and veratridine are consistent with reported effects of K-poor solutions in indicating that elevation of intracellular Na can lead to enhancement of Isi. Additional experiments suggest that the link between Nai and Ii involves intracellular Ca.6. When Cs-loaded Purkinje fibres were bathed in solutions containing Sr instead of Ca, enhancement of 18i by strophanthidin was abolished even though a positive inotropic response persisted.7. After intracellular injection of Purkinje fibres with EGTA, Ii no longer increased with strophanthidin, although it remained responsive to adrenaline.8. Clear-cut increases in IgE were seen in Cs-loaded Purkinje fibres even at very low concentrations of strophanthidin (20-50 nM), where the occurence of Na pump inhibition has been questioned.9. Positive regulation of Ca entry by intracellular Ca may act as a facilitory mechanism that amplifies myocardial responsiveness to digitalis and other inotropic interventions. Through changes in Ii, small rises in diastolic free Ca might lead to large increases in the activator Ca transient during contraction.

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“…Veratridine 4 and a monoester of germine, germine-3-acetate, 26 are known to have such an effect in nerve fibers. The rather long duration of the after-depolarization which the polyester germitrine induced in guinea pig papillary muscle was not unexpected, since Graham and Gasser 27 noted 45 years ago that protoveratrine, a mixture of two protoverine tetraesters, induces a longer lasting "negative after potential" in nerve than veratrine.…”

Section: Discussionmentioning

confidence: 99%

Sarcolemmal sodium permeability and contractile force of guinea pig papillary muscle: effects of germitrine.

Honerjäger¹,

Reiter²

1977

Circulation Research

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SUMMARY The action potential of guinea pig papillary muscle exposed to the ceveratrum alkaloid germitrine (2 J*M) is followed by a long-lasting after-depolarization (maximal amplitude, 8 mV; half-time of decay, 32 seconds; total duration, -75 seconds). This after-depolarization interrupts the terminal phase of repolarization. During repetitive stimulation (0.1-1.0 Hz; 80 nM germitrine) the after-depolarizations that follow consecutive action potentials are summed, causing persistent depolarization of up to 10 mV. The after-depolarization is reversibly abolished by tetrodotoxin (TTX). Test contractions evoked at various times during or after the germitrine-induced after-depolarization reveal a phase during which the ability of the muscle to develop force is transiently increased. This positive inotropic influence reaches its maximum 1 minute after the conditioning stimulus and thereafter decays with a half-time 4.8 times longer than the half-time of decay of the after-depolarization. It is reversibly abolished by TTX and augmented by dihydro-ouabain (DHO). We conclude: Germitrine induces an after-depolarization by prolonging dramatically the Na permeability component which is mediated by the fast Na channels and normally restricted to the first few milliseconds of the action potential. The germitrine-induced selective and persistent increase of sarcolemmal sodium permeability (P Na ) causes a positive inotropic effect, probably because intracellularly accumulating Na ions exchange for extracellular Ca ions.TWO DIFFERENT mechanisms are currently thought to play a major role in determining the inotropic state of the cardiac muscle cell: inward Ca current during depolarization, and Na-Ca exchange across the sarcolemma.1 The latter concept predicts that a change in the Na concentration gradient across the cell membrane alters the transsarcolemmal distribution of Ca. For instance, an increase of [Na]i at constant [Na] 0 should increase [Ca]|. Changes of [Na]j, by their effect on Na-Ca exchange, may be responsible for the positive inotropic response of cardiac muscle to increased stimulation rates or to cardiac glycosides. With regard to the functional significance of Na-Ca exchange it seemed desirable to test how an intervention which selectively increases the Na permeability (P Na ) of the sarcolemma affects contractile force.The ceveratrum alkaloid veratridine increases P Na of excitable membranes by a specific interaction with the (fast) Na channels. 4 The tetrodotoxin-sensitive prolongation of the cardiac action potential by veratrine 5 or veratridine 6 indicates that a drug-induced increase of P,\ a occurs during each excitation. If an increased sarcolemmal P,va causes a positive inotropic effect via accumulation of Na ions inside the cell, the inotropic response should lag behind the increase in P Na . The test of this prediction is complicated, however, by the relatively short duration of the Na permeability increase associated with veratrine or veratridine. The present publication shows that the germine triest...

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Electrophysiological effects of various ceveratrum alkaloids on single nerve axons

Cited by 23 publications

References 23 publications

Effects of Strophanthidin on the Slow Inward Current in Guinea‐pig Isolated Ventricular Myocytes

Effects of Strophanthidin on the Slow Inward Current in Guinea‐pig Isolated Ventricular Myocytes

Enhancement of calcium current during digitalis inotrophy in mammalian heart: positive feed‐back regulation by intracellular calcium?

Sarcolemmal sodium permeability and contractile force of guinea pig papillary muscle: effects of germitrine.

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