Calcium channel blockers prevent calcium from entering cells of the heart and blood vessel walls, resulting in lower blood pressure. Calcium channel blockers, also called calcium antagonists, relax and widen blood vessels by affecting the muscle cells in the arterial walls.
Calcium channels: background
The calcium channel has been proven essential for numerous biological processes from sarcomere shortening to neurotransmitter secretion. These channels are strictly responsible for the regenerative firing pattern in the muscles of many lower invertebrates such as arthropods, mollusks, nematodes, and in smooth muscle of vertebrates. In addition, they have been shown to coexist with sodium channels in many other types of cells where they partially contribute to electrical activity. For instance, Susumu Hagiwara and coworkers revealed that the action potential of vertebrate heart lasts for several milliseconds because of its use of calcium channels. In addition to nervous and muscle tissues. These channels have also been found to reside in all secretory gland cells where they regulate secretion. Thus, calcium channels are ubiquitous. Being found in all excitable cells. Without them, every excitable cell in organisms from planaria to people would have no output.
Calcium channels: pharmacology
Although it has been demonstrated that diverse biophysical parameters may be used to discriminate between T-, L-, and N-type calcium channels. A more stringent approach involving pharmacological agents has revealed an even more diverse calcium channel family than kinetic characteristics alone would disclose. Five groups of high voltage-activated calcium channels have been pharmacologically identified. These include L- and N-type channels. Whose identity was initially defined based on kinetics and then reconfirmed pharmacologically. β-type channels, Q-type channels and the most recently uncovered R-type channel. Which coincidentally displays resistance to all known and currently employed organic and peptide calcium channel antagonists.Calcium current was first identified in 1958 by Fatt and Ginsborg. And the concept of pharmacological calcium channel antagonists was proposed shortly thereafter by Fleckenstein in the 1960s. Since their scientific and clinical inception in the 1960’s and 1970s respectively. The list of compounds that specifically target voltage-dependent calcium channels has grown. However, only three classes of drugs have been found to faithfully discriminate between different calcium channel types.
Initially developed to treat high blood pressure and angina pectoris. The dihydropyridine (DHP) antagonists emerged as one of the most widely prescribed therapeutic agents in medicine. The most commonly employed DHP antagonists are nifedipine, nitrendipine and nimodipine. With their clinical effects most likely occurring due to inhibition of calcium channels in the smooth muscle of blood vessels and subsequent vasorelaxation. Experimental investigation has shown these drugs to petently inhibit L-type calcium channels in cardiac muscle, skeletal muscle, smooth muscle and neurons. For example, 1 μm nimodipine has been shown to completely inhibit the calcium channel current elicited by a depolarizing test step to -20 mV from a holding potential of -70 mV in a myocardial cell, a cell type whose calcium current is known to primarily consist of L-type current. At this concentration, it does not interact with P-type calcium channels in rat sympathetic neurons. Suggesting a high degree of specificity for L-type channels over other channel types. A drawback of DHP block of L-type channels is that the drugs may act with a higher potency when current is elicited from depolarized holding potentials. Where the channels are partly inactivated. Rather than from hyperpolarized holding potentials. Thus, DHP antagonists appear to bind with a high affinity to the inactivated state of the channel. But more weakly to the resting state of the channel. In addition to L-type channels being potently blocked by DHP antagonists. DHP agonists facilitate current flow specifically through L-type channels. Further solidifying the pharmacological identity of these channels as a distinct group.
Carter, T. J. (2002). Calcium channel modulation by GABA (B) receptor activation.