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Basic cellular mechanisms of action of the calcium-channel blockers
Insights
Calcium-channel blockers prevent calcium ion entry into heart and smooth muscle cells. This action affects heart contractility and conduction, particularly in the sinoatrial and atrioventricular nodes.
Area of Science:
- Cardiovascular Pharmacology
- Cell Physiology
Background:
- Calcium ions (Ca++) are crucial intracellular messengers in excitable cells.
- Calcium channels regulate Ca++ entry into cardiac and smooth muscle cells.
Purpose of the Study:
- To explain the effects of calcium-channel blockers on cardiac and vascular smooth muscle.
- To elucidate the mechanisms of calcium channel blockade.
Main Methods:
- Review of existing literature on calcium-channel blockers.
- Analysis of the electrophysiological effects on cardiac tissues.
- Discussion of molecular interactions with calcium channels.
Main Results:
- Calcium-channel blockers inhibit Ca++ entry, impacting myocardial contractility and AV nodal conduction.
- Conduction in the His-Purkinje system remains unaffected due to sodium-dependent action potentials.
- Different blockers exhibit varied interactions with sarcolemmal calcium channel proteins.
Conclusions:
- Calcium-channel blockers have distinct effects on cardiac and vascular tissues.
- Further research is needed to understand the molecular mechanisms of calcium channel blockade.
Abstract:
Calcium-channel blockers inhibit the entry of calcium ion (Ca++) into excitable cells, including those of coronary and peripheral arterial smooth muscle and the heart. The ability of these drugs to block Ca++ entry into cells inhibits the essential role of this cation as an intracellular messenger. The effects of calcium-channel blockers on the heart include a negative inotropic effect on the working myocardial cells of the atria and ventricles. Because the up-stroke of the action potential in these regions of the heart, and in the rapidly conducting cells of the His-Purkinje system, is due to a fast, sodium-dependent ionic current, calcium-channel blockers do not inhibit conduction in these cells. In the sinoatrial and atrioventricular (AV) nodes, on the other hand, depolarization is due primarily to a Ca++-dependent slow inward current; as a result, the calcium-channel blockers inhibit the sinus pacemaker and AV conduction. Because our knowledge of the molecular structure of the calcium channels in the heart and smooth muscle is rudimentary, little is known of the molecular mechanisms by which calcium-channel blockers inhibit Ca++ entry across the sarcolemmal membranes in these cells. It is apparent, however, that the actions of different members of this class of drugs on the sarcolemma are not the same. Indirect evidence indicates that some members of this class of drugs may interact with hydrophobic regions of the proteins that make up, or regulate, the calcium channels in the plasma membrane.(ABSTRACT TRUNCATED AT 250 WORDS)