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Interaction between Ca(2+) channel blockers and isoproterenol on L-type Ca(2+) current in canine ventricular
V Farkas1, N Szentandrássy, L Bárándi
1Department of Dentistry, University of Debrecen, Debrecen, Hungary.
Aim:
The aim of this work was to study antagonistic interactions between the effects of various types of Ca(2+) channel blockers and isoproterenol on the amplitude of L-type Ca(2+) current in canine ventricular cells.
Methods:
Whole-cell version of the patch clamp technique was used to study the effect of isoproterenol on Ca(2+) current in the absence and presence of Ca(2+) channel-blocking agents, including nifedipine, nisoldipine, diltiazem, verapamil, CoCl(2) and MnCl(2) .
Results:
Five micromolar Nifedipine, 1 μM nisoldipine, 10 μM diltiazem, 5 μM verapamil, 3 mM CoCl(2) and 5 mM MnCl(2) evoked uniformly a 90-95% blockade of Ca(2+) current in the absence of isoproterenol. Isoproterenol (100 nM) alone increased the amplitude of Ca(2+) current from 6.8 ± 1.3 to 23.7 ± 2.2 pA/pF in a reversible manner. Isoproterenol caused a marked enhancement of Ca(2+) current even in the presence of nifedipine, nisoldipine, diltiazem and verapamil, but not in the presence of CoCl(2) or MnCl(2) .
Conclusion:
The results indicate that the action of isoproterenol is different in the presence of organic and inorganic Ca(2+) channel blockers. CoCl(2) and MnCl(2) were able to fully prevent the effect of isoproterenol on Ca(2+) current, while the organic Ca(2+) channel blockers failed to do so. This has to be born in mind when the effects of organic Ca(2+) channel blockers are evaluated either experimentally or clinically under conditions of increased sympathetic tone.
Insights
Isoproterenol enhances L-type calcium current, but its effect is blocked by inorganic agents (CoCl2, MnCl2), not organic calcium channel blockers. This highlights differing drug interactions under sympathetic stimulation.
Area of Science:
- Cardiovascular Physiology
- Pharmacology
- Cellular Electrophysiology
Background:
- Calcium (Ca2+) channels are crucial for cardiac function.
- Isoproterenol is a beta-adrenergic agonist that modulates Ca2+ current.
- Calcium channel blockers are used to treat cardiovascular diseases.
Purpose of the Study:
- To investigate the antagonistic interactions between calcium channel blockers and isoproterenol.
- To determine the effect of various Ca2+ channel blockers on L-type Ca2+ current amplitude in canine ventricular cells.
Main Methods:
- Utilized the whole-cell patch clamp technique.
- Studied the impact of isoproterenol on Ca2+ current.
- Examined effects in the presence and absence of nifedipine, nisoldipine, diltiazem, verapamil, cobalt chloride (CoCl2), and manganese chloride (MnCl2).
Main Results:
- Organic Ca2+ channel blockers (nifedipine, nisoldipine, diltiazem, verapamil) and inorganic blockers (CoCl2, MnCl2) all caused significant blockade of Ca2+ current.
- Isoproterenol alone increased Ca2+ current amplitude.
- Isoproterenol enhanced Ca2+ current in the presence of organic blockers but not inorganic blockers (CoCl2, MnCl2).
Conclusions:
- Isoproterenol's action differs depending on the type of Ca2+ channel blocker.
- Inorganic blockers (CoCl2, MnCl2) fully prevented isoproterenol's effect on Ca2+ current.
- Organic blockers did not prevent isoproterenol's effect, suggesting different interaction mechanisms relevant for clinical and experimental evaluations during sympathetic activation.
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