Calcium Channels in the Heart: Disease States and Drugs

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.

Keywords: arrhythmia; calcium channel blockers; calcium channels; calcium ions; cardiac function.

Figure 1

Schematic representation of the calcium channels: Calcium channels are a complex of 4–5 distinct subunits. The α1 subunit is the largest subunit and it incorporates the pore region, the voltage sensor and gating apparatus, several channel regulation sites by second messengers, drugs, and toxins. There is an intracellular β subunit, a transmembrane, α2δ subunit complex, and a transmembrane γ subunit.

Figure 2

Charts represent the types of calcium channels in the heart, their function and the dysfunctions they are associated with. (A). L-Type channels, (B). T-type channels.

Figure 2

Charts represent the types of calcium channels in the heart, their function and the dysfunctions they are associated with. (A). L-Type channels, (B). T-type channels.