The effect of D600 on tonic tension, Na+ inward current, and Na+–Ca2+ exchange in frog heart

1985 ◽  
Vol 63 (11) ◽  
pp. 1404-1410 ◽  
Author(s):  
Magda Horackova
Keyword(s):  
Calcium Channel ◽  
Positive Inotropic Effect ◽  
Channel Blocker ◽  
High Amplitude ◽  
Inhibitory Effect ◽  
Frog Heart ◽  
Tonic Component ◽  
Inward Current ◽  
Tonic Tension ◽  
Calcium Inward Current

Preparations of frog atrial muscle were stimulated at 0.33 Hz under voltage clamp, and the resulting membrane currents and the twitch contractions (phasic and tonic components) were recorded in presence or absence of D600. It has been suggested earlier that the tonic contractions are regulated by an electrogenic Na+–Ca2+ exchange, while the phasic contractions are closely related to the calcium inward current (Isi). In this study we investigated the effect of D600 on (i) the tonic contractions elicited by long depolarizing pulses of high amplitude and (ii) the tonic contractions increased by veratrine and resulting in a positive inotropic effect (PIE). While 1 μM D600 reduced Isi and the corresponding phasic contractions to < 30% of their initial values within 5 min, the inhibitory effect of D600 on tonic contractions developed more slowly or higher concentrations of D600 were needed to achieve similar levels of inhibition within the same time. Furthermore, applications of 5–50 μM D600 inhibited the veratrine-induced increase in INa and in tonic contractions, and both of these effects again fully developed within a few minutes of D600 being removed. The results demonstrate that D600 inhibits not only Isi and phasic contractions, but it also decreases the tonic contractions in frog heart. The effect on the tonic component is associated with inhibition of the tetrodotoxin-sensitive Na+ inward current, and the results are interpreted as an effect of D600 on the electrogenic Na+–Ca2+ exchange. These additional effects of D600 should be considered when using this drug as the "specific" calcium channel blocker.

Analysis of catecholamine effects in single atrial trabeculae of the frog heart

1977 ◽  
Vol 197 (1128) ◽  
pp. 333-362 ◽  
Keyword(s):  
Cell Membrane ◽  
Action Potential ◽  
Time Course ◽  
Drug Exposure ◽  
Drug Application ◽  
Latency Period ◽  
Frog Heart ◽  
Phosphodiesterase Activity ◽  
Inward Current ◽  
Calcium Inward Current

A study was made of the time course of the effects of adrenaline and isoprenaline on both twitch tension and the intracellular action potential of single atrial trabeculae from frog heart, under a variety of experimental conditions. Twitch tension and overshoot of action potentials rose and subsided in a parallel fashion during build-up and decline of catecholamine action. Cessation of stimulation during drug application had little effect on the tension responses to the drugs. These, and also results obtained with step changes of external calcium concentration during drug exposure, suggest that tension enhancement is a direct consequence of the increased calcium inward current produced by the catecholamines. Exceptional results from trabeculae of ‘hypodynamic’ hearts are described and interpreted on the basis of previous findings obtained in the ‘hypo-dynamic’ condition. Under suitable conditions, including the use of brief periods of drug exposure (≤20 s), three phases of ( β -catecholamine action were discernible: (1) a latency period, of up to 15 s, which preceded tension and potential rise after drug application. Results are presented suggesting that this latency mainly reflects the time which it takes for drug-combined receptors to activate adenylate cyclase in the cell membrane. (2) A sub­sequent phase was critically dependent, in both its magnitude and time course, on phosphodiesterase activity, as was shown by the application of the specific inhibitors papaverine, ICI 63 197, and Ro 20-1724. This phase is probably controlled by the build-up and decline of cAMP within the cells and the subsequent activation and deactivation of a protein kinase. (3) A third phase, associated with the final portion of the decline of catecholamine action, was relatively insensitive to moderate inhi­bition of phosphodiesterase activity. It is attributed to a change of phosphorylation of sites at the internal surface of the cell membrane, the process which, it is assumed, determines the size of calcium inward current during an action potential. Tension decline after a short staircase occurred with a time course closely similar to that of the final phase of the declining catecholamine response. A common final step in the sequential cellular processes under­ lying the two responses is proposed. In some 40% of the trabeculae examined, adrenaline responses were of ‘mixed’ origin: in addition to the relatively slow β -adrenergic action, an initial rapid tension change was present, and experimental tests suggest that this is mediated by α -type receptors.

scholarly journals Agatoxin-IVA-Sensitive Calcium Channels Mediate the Presynaptic and Postsynaptic Nicotinic Activation of Cardiac Vagal Neurons

2001 ◽  
Vol 85 (1) ◽  
pp. 164-168 ◽  
Author(s):  
Jijiang Wang ◽  
Mustapha Irnaten ◽  
David Mendelowitz
Keyword(s):  
Calcium Channels ◽  
Calcium Channel ◽  
Calcium Channel Blocker ◽  
Channel Blocker ◽  
Patch Clamp Technique ◽  
Current Increase ◽  
Inward Current ◽  
Voltage Dependent Calcium Channel ◽  
Voltage Dependent ◽  
Voltage Dependent Calcium Channels

Whole cell currents and miniature glutamatergic synaptic events (minis) were recorded in vitro from cardiac vagal neurons in the nucleus ambiguus using the patch-clamp technique. We examined whether voltage-dependent calcium channels were involved in the nicotinic excitation of cardiac vagal neurons. Nicotine evoked an inward current, increase in mini amplitude, and increase in mini frequency in cardiac vagal neurons. These responses were inhibited by the nonselective voltage-dependent calcium channel blocker Cd (100 μM). The P-type voltage-dependent calcium channel blocker agatoxin IVA (100 nM) abolished the nicotine-evoked responses. Nimodipine (2 μM), an antagonist of L-type calcium channels, inhibited the increase in mini amplitude and frequency but did not block the ligand gated inward current. The N- and Q-type voltage-dependent calcium channel antagonists conotoxin GVIA (1 μM) and conotoxin MVIIC (5 μM) had no effect. We conclude that the presynaptic and postsynaptic facilitation of glutamatergic neurotransmission to cardiac vagal neurons by nicotine involves activation of agatoxin-IVA-sensitive and possibly L-type voltage-dependent calcium channels. The postsynaptic inward current elicited by nicotine is dependent on activation of agatoxin-IVA-sensitive voltage-dependent calcium channels.

Effect of the organic Ca2+ channel blocker D-600 on sarcoplasmic reticulum Ca2+ uptake in skeletal muscle

1997 ◽  
Vol 272 (1) ◽  
pp. C310-C317 ◽  
Author(s):  
A. Ortega ◽  
H. Gonzalez-Serratos ◽  
J. R. Lepock
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Calcium Channel ◽  
Channel Blocker ◽  
Inhibitory Effect ◽  
Blocking Effect ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
Dose Dependent ◽  
Caffeine Exposure

Experiments were undertaken to study the possibility that the calcium channel blocker D-600 (gallopamil), which penetrates into muscle cells (20), facilitates excitation-contraction coupling in skeletal muscle (7) by a direct effect on the sarcoplasmic reticulum (SR). The effects of D-600 were studied on single phasic muscle fibers, either intact or split open. D-600 potentiated twitches in intact fibers at concentrations lower than those reported in whole muscles. In split fibers, the force produced by caffeine-induced Ca2+ release from the SR was reversibly inhibited by 5 microM D-600, when added to the Ca2+ loading solution. This inhibitory effect was inversely related to temperature, and it was dose dependent. When D-600 was added after Ca2+ loading and before caffeine exposure, or during the caffeine exposure itself, it did not inhibit Ca2+ release, but rather increased the development of force. We conclude that, apart from the blocking effect that D-600 may have on the voltage sensor, the drug penetrates into the myoplasm and affects excitation-contraction coupling by inhibiting the SR Ca2+ pump. This may be the consequence of a conformational change in the transmembrane Ca2+ binding domain of the ATPase.

Chronic treatment by the calcium channel blocker ± PN 200-110 in the rat counteracts the stimulations of pituitary weight, prolactin release and pituitary C-kinase activity induced by a chronic estradiol treatment, in vivo

1990 ◽  
Vol 122 (3) ◽  
pp. 403-408
Author(s):  
Ph. Touraine ◽  
P. Birman ◽  
F. Bai-Grenier ◽  
C. Dubray ◽  
F. Peillon ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Calcium Channel ◽  
Calcium Channel Blocker ◽  
Channel Blocker ◽  
Plasma Prolactin ◽  
Estradiol Treatment ◽  
Kinase C ◽  
Protein Kinase C Activity

Abstract In order to investigate whether a calcium channel blocker could modulate the protein kinase C activity in normal and estradiol pretreated rat pituitary, female Wistar rats were treated or not (controls) with ± PN 200-110 (3 mg · kg−1 · day−1, sc) for 8 days or with estradiol cervical implants for 8 or 15 days, alone or in combination with PN 200-110 the last 8 days. Estradiol treatment induced a significant increase in plasma prolactin levels and pituitary weight. PN 200-110 administered to normal rats did not modify these parameters, whereas it reduced the effects of the 15 days estradiol treatment on prolactin levels (53.1 ± 4.9 vs 95.0 ±9.1 μg/l, p<0.0001) and pituitary weight (19.9 ± 0.4 vs 23.0 ± 0.6 mg, p <0.001), to values statistically comparable to those measured after 8 days of estradiol treatment. PN 200-110 alone did not induce any change in protein kinase C activity as compared with controls. In contrast, PN 200-110 treatment significantly counteracted the large increase in soluble activity and the decrease in the particulate one induced by estradiol between day 8 and day 15. We conclude that PN 200-110 opposed the stimulatory effects of chronic in vivo estradiol treatment on plasma prolactin levels and pituitary weight and that this regulation was related to a concomitant modulation of the protein kinase C activity.

Effects of an Antihypertensive Combination in Japanese Hypertensive Outpatients Based on the Long-Acting Calcium Channel Blocker Benidipine on Vascular and Renal Events: A Sub-Analysis of the COPE Trial

2020 ◽  
Vol 16 ◽  
Author(s):  
Seiji Umemoto ◽  
Toshio Ogihara ◽  
Masunori Matsuzaki ◽  
Hiromi Rakugi ◽  
Kazuyuki Shimada ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Calcium Channel ◽  
Calcium Channel Blocker ◽  
Channel Blocker ◽  
Rank Test ◽  
Vascular Events ◽  
Treatment Groups ◽  
Β Blocker ◽  
The Difference ◽  
Long Acting

Background: In the trial known as COPE (Combination Therapy of Hypertension to Prevent Cardiovascular Events) three benidipine (a calcium channel blocker; CCB) regimens were compared. Hypertensive Japanese outpatients aged 40–85 years (n=3,293) who did not achieve the target blood pressure of <140/90 mmHg with benidipine 4 mg/day were treated with the diuretic thiazide (n=1,094) or a β-blocker (n=1,089) or an additional angiotensin receptor blocker (ARB; n=1,110). A significantly higher incidence of hard cardiovascular composite endpoints and of fatal or non-fatal strokes was observed in the benidipine-β-blocker group compared to the benidipine-thiazide group. Objective and Methods: We further evaluated the treatment effects of the three benidipine-based regimens on vascular and renal events in a sub-analysis of the COPE patients. Results: A total of 10 vascular events (0.8 per 1,000 person-years) including one aortic dissection (0.1 per 1,000 person-years) and nine cases of peripheral artery disease (0.8 per 1,000 person-years) were documented, as was a total of seven renal events (0.6 per 1,000 person-years). No significant differences in vascular and renal events were revealed among the three treatment groups: vascular events p=0.92 renal events p=0.16 log-rank test. Conclusions: Blood pressure-lowering therapy with benidipine combined with an ARB, β-blocker, or thiazide was similarly effective in the prevention of vascular and renal events in hypertensive outpatients, although there is no enough these events to compare the difference in the three treatment groups.

Electroanalytical Methods for Determination of Calcium Channel Blockers

2019 ◽  
Vol 15 (3) ◽  
pp. 207-218 ◽  
Author(s):  
Fatma Ağın
Keyword(s):  
Calcium Channel ◽  
Calcium Channel Blockers ◽  
Channel Blocker ◽  
Heart Diseases ◽  
Dosage Forms ◽  
Channel Blockers ◽  
Electroanalytical Methods ◽  
Pharmaceutical Dosage Forms ◽  
Ischemic Heart Diseases

Background:Calcium Channel Blockers (CCBs) are widely used in the treatment of cardiovascular and ischemic heart diseases in recent years. They treat arrhythmias by reducing cardiac cycle contraction and also benefit ischemic heart diseases. Electroanalytical methods are very powerful analytical methods used in the pharmaceutical industry because of the determination of therapeutic agents and/or their metabolites in clinical samples at extremely low concentrations (10-50 ng/ml). The purpose of this review is to gather electroanalytical methods used for the determination of calcium channel blocker drugs in pharmaceutical dosage forms and biological media selected mainly from current articles.Methods:This review mainly includes recent determination studies of calcium channel blockers by electroanalytical methods from pharmaceutical dosage forms and biological samples. The studies of calcium channel blockers electroanalytical determination in the literature were reviewed and interpreted.Results:There are a lot of studies on amlodipine and nifedipine, but the number of studies on benidipine, cilnidipine, felodipine, isradipine, lercanidipine, lacidipine, levamlodipine, manidipine, nicardipine, nilvadipine, nimodipine, nisoldipine, nitrendipine, diltiazem, and verapamil are limited in the literature. In these studies, DPV and SWV are the most used methods. The other methods were used less for the determination of calcium channel blocker drugs.Conclusion:Electroanalytical methods especially voltammetric methods supply reproducible and reliable results for the analysis of the analyte. These methods are simple, more sensitive, rapid and inexpensive compared to the usually used spectroscopic and chromatographic methods.

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