Name: Antihypertensive Drugs: Action of Calcium Channel Blockers
Uploaded: 2024-10-11T14:09:27
Description: Calcium ions are essential to contract smooth muscle cells in blood vessels. They enter these cells through voltage-dependent calcium channels, ...

Vascular smooth muscle cells feature L-type voltage-gated calcium channels in their plasma membrane.
Upon depolarization, these channels open, and Ca2+ flow into the cell.
This influx prompts repolarization, closing the channels and preventing further ion entry.
The ions stimulate the ryanodine receptor, causing a larger calcium release from the sarcoplasmic reticulum.
This activates calmodulin to form a complex that activates myosin light-chain kinase.
This phosphorylates the myosin light chain, enabling interaction between actin and myosin. As a result, the smooth muscles contract.
However, overactive L-type calcium channels can cause excessive calcium entry into the cells, leading to prolonged vasoconstriction and elevated blood pressure.
Calcium channel blockers, such as amlodipine, block the &#593;1 subunit of these channels, inhibiting Ca2+ entry into the cell.
This action lowers intracellular calcium levels, relaxing the arterial smooth muscles, reducing peripheral resistance, and ultimately decreasing blood pressure.

antihypertensive drugs: action of calcium channel blockers

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 &#945;1 subunit of the calcium channels, inhibiting calcium ions&#39; 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.