Calcium ions are essential to contract smooth muscle cells in blood vessels. They enter these cells through voltage-dependent calcium channels, specifically L-type calcium channels in the cell membrane. These L-type calcium channels are integral to the excitation-contraction coupling process in smooth muscle. When a stimulus is received by smooth muscle cells, their membrane depolarizes. This alteration in membrane potential instigates the opening of L-type calcium channels. As a result, calcium ions are allowed to enter the cell from the external environment. The resulting increase in intracellular calcium concentration activates calmodulin, a protein that binds calcium. Calmodulin then binds to and activates myosin-light chain kinase (MLCK), which phosphorylates the light chain. This phosphorylation allows myosin to interact with actin, initiating cross-bridge cycling and culminating in smooth muscle contraction. However, if L-type calcium channels become overactive, it can lead to an excessive influx of calcium into vascular smooth muscle cells. This leads to higher cytosolic calcium levels, which can extend vasoconstriction, thereby increasing peripheral resistance and raising blood pressure. Calcium channel blockers, such as dihydropyridines like amlodipine, nicardipine, and felodipine, block these voltage-gated calcium channels. They attach to the α1 subunit of the calcium channels, inhibiting calcium ions' entry into the cell. This action leads to a decrease in intracellular calcium concentration, weakening muscle cell contractions. This relaxation of arterial smooth muscle cells reduces peripheral resistance and blood pressure.
