L-type calcium channel (dihydropyridine receptor) (DHPR)

The dihydropyridine binding site is a well-defined structural region on the alpha1 subunit of the L-type voltage-gated calcium channel, which is also termed the dihydropyridine receptor (DHPR). The DHPR is a multisubunit complex essential for allowing calcium influx into cells in response to depolarization, which triggers muscle contraction in skeletal, cardiac, and some smooth muscles, and plays vital roles in neuronal signaling. The receptor complex includes the pore-forming alpha1 subunit (which houses the DHP binding site and forms the actual ion channel), several auxiliary subunits (alpha2/delta, beta, gamma), and interacts physically with the ryanodine receptor in skeletal muscle for excitation-contraction coupling. The DHP binding site resides within the transmembrane regions of the alpha1 subunit (particularly IIIS5, IIIS6, IVS6), and binding of drugs such as nifedipine stabilizes a non-conducting state of the channel to block calcium influx. Due to its central role in calcium homeostasis, the DHPR is a major therapeutic target in cardiovascular and other diseases.

Other names

Dihydropyridine receptorL-type calcium channelL-type voltage-gated calcium channelCav1.1 (skeletal muscle)Cav1.2 (cardiac/smooth muscle, neurons)Cav1.3Cav1.4DHPR

Dihydropyridines (DHPs): bind to the DHP binding site on the alpha1 subunit, preferentially stabilizing the inactivated (non-conducting) state of the channel, thereby reducing calcium entry. Phenylalkylamines and benzothiazepines: bind to distinct but allosterically linked receptor sites, modulating channel opening and frequency dependence.