Calcium channels in the heart.

The primary mechanism of action of calcium antagonists is to inhibit the ion channel in the cell membrane, which allows the slow influx of calcium into the cell in a variety of tissues. In vascular smooth muscle this results in a reduction of tone, producing vasodilatation. In the heart, calcium antagonists cause vasodilatation of the coronary vessels, thus increasing coronary blood flow, and reduce myocardial contractility, which in turn reduces myocardial oxygen consumption. These haemodynamic effects may be beneficial in myocardial ischaemia. The increase in cytosolic calcium required for contraction of the myofibrils is a result of two mechanisms, the slow influx of calcium followed by the further release of calcium from the lateral cysternae (a specialized part of the sarcoplasmic reticulum) within the cell. Calcium antagonists block the slow influx of calcium by occupying binding sites on the outside of the membrane channel but do not affect the release of calcium from the sarcoplasmic reticulum. Subtle changes in these channels may occur during ischaemia, with a rise in cytosolic calcium occurring early, followed by a further influx in calcium on reperfusion. Calcium antagonists inhibit the calcium rise on reperfusion if applied before ischaemia but not when added at the time of reperfusion. Calcium antagonists have not been shown to reduce infarct size. Their major role is in chronic angina and hypertension. Future possible indications may include the treatment of asymptomatic ischaemia, mild heart failure or ischaemic events prior to a myocardial infarction.