Abstract
Calcium ions are the major signaling ions in the cells. They regulate muscle contraction, neurotransmitter secretion, cell growth and migration, and the activity of several proteins including enzymes and ion channels and transporters. They participate in various signal transduction pathways, thereby regulating major physiological functions. Calcium ion entry into the cells is regulated by specific calcium channels and transporters. There are mainly six types of calcium channels, of which only two are prominent in the heart. In cardiac tissues, the two types of calcium channels are the L type and the T type. L-type channels are found in all cardiac cells and T-type are expressed in Purkinje cells, pacemaker and atrial cells. Both these types of channels contribute to atrioventricular conduction as well as pacemaker activity. Given the crucial role of calcium channels in the cardiac conduction system, mutations and dysfunctions of these channels are known to cause several diseases and disorders. Drugs targeting calcium channels hence are used in a wide variety of cardiac disorders including but not limited to hypertension, angina, and arrhythmias. This review summarizes the type of cardiac calcium channels, their function, and disorders caused by their mutations and dysfunctions. Finally, this review also focuses on the types of calcium channel blockers and their use in a variety of cardiac disorders.
Highlights
Introduction to Cardiac Calcium Channels Mammalian hearts are four-chambered with two atria and ventricles each
Several types of ion channels function in cardiac cells as complexes, partnering with other proteins, and generate cardiac action potential [4–6]
This review explores the types of calcium channels in the heart (L-type and T-type), their structure and function, associated disorders, and the pharmacological advances targeting cardiac calcium channels
Summary
There have been six classes of calcium channels identified so far, based on the rate of their activation, pharmacologic sensitivity, and the level of voltage activation (low or high voltage). Much like the L-type calcium channels, the pore-forming region is the connecting segments of S5 and S6 This region contains four key acidic residues, including glutamate or aspartate [26]. It forms a tetrameric structure composed of the four domains and is lined by the S5– S6 linkers, known as the p-loops [27]. The arrangement of these residues is responsible for The arrangement of these residues is responsible for the selectivity of T-type calcium channels [26]. Cacnb and Cacnb are enriched in the conduction system [29] and T-type channels are enriched in the adult SAN and AV node [30]
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