Calcium Channel

Voltage-gated calcium channels are required for key functions in excitable cells, including transmitter release and hormone secretion, excitation-transcription coupling, and excitation-contraction coupling. The first voltage-gated calcium channel complex to be studied was that from skeletal muscle, where it is present in great abundance in the transverse tubules. After purification of the complex, it was found to contain five components: α1 (approximately 170 kDa), α2 (approximately 150 kDa), β (approximately 52 kDa), δ (approximately 17–25 kDa), and γ (approximately 32 kDa) in an approximately stoichiometric ratio.  
Current therapeutic agents include drugs targeting L-type CaV1.2 calcium channels, particularly 1,4-dihydropyridines, which are widely used in the treatment of hypertension. T-type (CaV3) channels are a target of ethosuximide, widely used in absence epilepsy. The auxiliary subunit α2δ-1 is the therapeutic target of the gabapentinoid drugs, which are of value in certain epilepsies and chronic neuropathic pain. The limited use of intrathecal ziconotide, a peptide blocker of N-type (CaV2.2) calcium channels, as a treatment of intractable pain, gives an indication that these channels represent excellent drug targets for various pain conditions.  
The recent discovery of important physiologic functions differentially controlled by CaV1.2 and CaV1.3 identifies both channels as potentially novel drug targets, if selectivity can be achieved. Nonselective blockers of these channels (DHPs and other CCBs) have been of use in the treatment of hypertension for many years and their side effect profile has been well studied. Some selectivity of DHPs is nevertheless achieved in vivo for targeting vascular CaV1.2 because of the depolarized potentials found in this tissue, since DHPs bind with higher affinity to inactivated channels. If selective drugs can be developed, there is a strong therapeutic potential for selective CaV1.3 blockers for several indications, including neuropsychiatric diseases, PD neuroprotection, and resistant hypertension associated with hyperaldosteronism.


1.Gerald W. Zamponi,et al. Pharmacol Rev. 2015 Oct; 67(4): 821–870.