Inhibition of the slow inward current by nifedipine in mammalian ventricular myocardium

Kohlhardt, M.; Fleckenstein, A.

doi:10.1007/bf00500899

Cited by 188 publications

(55 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Similar findings have been obtained with diltiazem (Tung & Morad, 1983;Lee & Tsien, 1983) whereas findings have been less clear with dihydropyridine antagonists, such as nifedipine, nisoldipine, nitrendipine and nicardipine, which have variously been shown to exhibit little voltage-dependence (e.g. Kohlhardt & Fleckenstein, 1977;Bayer & Ehara, 1978;Tung & Morad, 1983) or, in a recent study in calf Purkinje fibres using a voltage clamp technique, to show clear voltage-dependence (Sanguinetti & Kass, 1984). The results in the present study confirm the voltage-dependent responses to verapamil and to the dihydropyridine, nifedipine.…”

Section: Discussionsupporting

confidence: 66%

Evidence that oxmetidine inhibits transmembrane calcium flux in cardiac and vascular tissue

Gristwood¹,

Jim²,

Macia³

et al. 1985

British J Pharmacology

View full text Add to dashboard Cite

Oxmetidine, at concentrations in excess of 1 times 10−6M, caused concentration‐dependent negative inotropic and chronotropic responses in guinea‐pig isolated heart preparations. Oxmetidine, at concentrations in excess of 1 times 10−5M, caused negative inotropic responses in guinea‐pig papillary muscle preparations. The negative inotropic responses to oxmetidine were associated with shortening of the plateau phase of the action potential. Verapamil and nifedipine caused similar shortening of the plateau phase of the action potential at equivalent negative inotropic concentrations indicating that oxmetidine may also act as a calcium antagonist. In preparations partially depolarized by raising extracellular K+ concentration, oxmetidine also exhibited negative inotropic activity and reduced the calcium‐dependent action potential. However, unlike verapamil and nifedipine, oxmetidine did not show voltage‐dependent activity. Oxmetidine, at concentrations in excess of 1 times 10−5M, inhibited Ca2+‐dependent contractions of dog saphenous vein preparations and inhibited 45Ca2+‐uptake into veins depolarized by high extracellular K+. In vivo, these calcium antagonist actions of oxmetidine were demonstrated by vasodilatation, reduction in blood pressure, bradycardia and reduced cardiac output in anaesthetized cats. Oxmetidine, at concentrations of 1 times 10−5M and above, shows properties consistent with inhibition of transmembrane Ca2+ flux. This action can be distinguished from other calcium antagonists as the effects of oxmetidine are not voltage‐dependent.

show abstract

Section: Discussionsupporting

confidence: 66%

Evidence that oxmetidine inhibits transmembrane calcium flux in cardiac and vascular tissue

Gristwood¹,

Jim²,

Macia³

et al. 1985

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…Evidence for this was provided by our experiments with verapamil, a phenylalkylamine known to block L-type channels specifically (Bean, 1985;Koblhardt and Fleckenstein, 1977;Nilius et al, 1985). L-type channels stay open a long time, providing ample opportunity for a steady influx of Ca2+ once they are activated (Cognard et al, 1986a,b).…”

Section: Occlusion Is a Ca2+-dependent Processmentioning

confidence: 83%

“…Verapamil (VER) was used as a channel blocker (Bean, 1985;Koblhardt and Fleckenstein, 1977;Nilius et al, 1985), and ionophore A23187 (A231 was used to create pores specific to Ca2+ (Reed and Lardy, 1972). A series of experiments was done in which embryos were treated with blockers or enhancers of Ca2+ in Ca2 * -enriched or -depleted medium.…”

Section: This Brings Up the Interesting Question Of How Ca2mentioning

confidence: 99%

Second messenger regulation of occlusion of the spinal neurocoel in the chick embryo

Desmond

Duzy

Federici

1993

Developmental Dynamics

View full text Add to dashboard Cite

We know that, once rostra1 neurulation is completed in the neuroaxis of the chick embryo, the caudal neurocoel becomes occluded and the brain rapidly expands. However, very little is known about the mechanisms maintaining occlusion. Studies had shown that occluded neurocoels reopened in embryos treated with chelators of cations, but the reasons remained unclear and the cations unidentified. To begin defining the role of cations, this study explored the effect of CaZC, calmodulin, and cAMP on maintaining the occluded neurocoel. Chick embryos during the natural phase of neurocoel occlusion (stage 12) were cultured in vitro with drugs known to modulate Ca2+ transport, to inhibit calmodulin activity, or to elevate cAMP levels. To test if occlusion is a Ca2+-dependent process, embryos were treated with verapamil and ionophore A23187. To test if occlusion requires calmodulin, embryos were treated with antipsychotic agents. To test if occlusion is cAMP dependent, embryos were treated with methylisobutylxanthine (MIX), forskolin (FOR), or dibutyl cyclic adenosine (DbC). Following each treatment, occlusion of the neurocoel was tested by injecting dye into the midbrain. All treatments resulted in a predominant number of precocious reopenings of the occluded neurocoels. MIX-treated, naked neural tubes had a fourfold increase in CAMP, whereas FOR-and DbCtreated neural tubes showed ten-and 14-fold increases, respectively. The presence of calmodulin in the cells of the neural tube was confirmed by fluorescent tagging and 3H-chlorpromazine labelling. The combined results of this study show that occlusion of the spinal neurocoel depends on exogenous Ca2+, requires calmodulin, and is cAMP sensitive. 0 1993 Wiley-Liss, Inc.

show abstract

“…In view of the above results, it was therefore not surprising to find that the specific calcium channel inhibitors, nifedipine (Fleckenstein et al, 1972;Kohlhardt & Fleckenstein, 1977) and nisoldipine (Kass, 1982) both produced a marked inhibition of contractions elicited in depolarized preparations at concentrations which reduced dV/dt, amplitude and overshoot of the accompanying slow current action potentials. All these effects were reversed by increasing extracellular calcium concentration.…”

Section: Electrophysiological Effects In Depolarized Atriamentioning

confidence: 98%

Effects of selective channel blocking agents on contractions and action potentials in K⁺‐depolarized guinea‐pig atria

Brown¹,

Marshall²,

Winslow³

1985

British J Pharmacology

View full text Add to dashboard Cite

1 Contractions and transmembrane action potentials were induced by 1 gM isoprenaline in K+-depolarized guinea-pig left atria driven at 0.5 Hz. 2 The stability of these responses was significantly increased by doubling the extracellular glucose concentration to 22 mM. 3 Action potential overshoot increased by 28 mV per ten fold increase in extracellular calcium concentration suggesting that the inward current in this preparation is carried by Ca2+. 4 In depolarized driven preparations, nanomolar concentrations of nifedipine and nisoldipine reduced contractility, maximum rate of depolarization (dV/dt max) and action potential height, whereas the fast channel blocking agents tetrodotoxin and mexiletine (in micromolar concentrations) produced little change. Nifedipine also rendered spontaneously beating depolarized right atrial preparations quiescent. 5 In concentrations which reduced dV/dt of normal action potentials, the sodium channel blocking agents quinidine and Org 6001 reduced the amplitude of contractions and reduced the maximum rate ofphase 0 depolarization (dV/dt) ofaction potentials in depolarized tissue. These actions were reversed by Ca2+ and suggest calcium antagonistic activity. However action potential height was not reduced. Like bepridil, both drugs also reduced the frequency of spontaneous contractions in depolarized right atrial preparations. 6 Unlike Org 6001, quinidine failed to produce a shift in calcium log dose-response curves in driven depolarized preparations and induced positive inotropy in the presence of functional sodium channels. 7 Bepridil inhibited contractions in depolarized atria in the absence ofa reduction in dV/dt suggesting that any calcium antagonistic action in atrial tissue is mainly located at an intracellular site. 8 In conclusion, action potentials elicited by isoprenaline in potassium-depolarized atria bathed in high glucose appear to be Ca2+ mediated. In concentrations which inhibit the inward Na+ current, both quinidine and Org 6001 exhibit calcium channel blocking properties.

show abstract

Inhibition of the slow inward current by nifedipine in mammalian ventricular myocardium

Cited by 188 publications

References 6 publications

Evidence that oxmetidine inhibits transmembrane calcium flux in cardiac and vascular tissue

Evidence that oxmetidine inhibits transmembrane calcium flux in cardiac and vascular tissue

Second messenger regulation of occlusion of the spinal neurocoel in the chick embryo

Effects of selective channel blocking agents on contractions and action potentials in K⁺‐depolarized guinea‐pig atria

Contact Info

Product

Resources

About

Inhibition of the slow inward current by nifedipine in mammalian ventricular myocardium

Cited by 188 publications

References 6 publications

Evidence that oxmetidine inhibits transmembrane calcium flux in cardiac and vascular tissue

Evidence that oxmetidine inhibits transmembrane calcium flux in cardiac and vascular tissue

Second messenger regulation of occlusion of the spinal neurocoel in the chick embryo

Effects of selective channel blocking agents on contractions and action potentials in K+‐depolarized guinea‐pig atria

Contact Info

Product

Resources

About

Effects of selective channel blocking agents on contractions and action potentials in K⁺‐depolarized guinea‐pig atria