shows that only the N-type calcium channel, not the P/Q/L type calcium channels, are involved in the release of norepinephrine. In the kidneys, blocking of N-type calcium channels reduce glomerular pressure through dilation of arterioles. N-type calcium channels have been shown to play a part in the localization of neurite growth in the sympathetic nervous system and the skin and spinal cord. The neurite outgrowth was shown to be inhibited through an interaction between laminin and the 11th loop of the n-type calcium channel structure. It has been suggested that neurites outgrowth is inhibited by the influx of calcium through the growth cone, and this happens when the Cav2.2 channel comes in contact with laminin 2, and in response can induce a stretch activation of the N-type calcium channel. Mutations A rare gain-of-function mutation in CACNA1B gene encoding the α1B subunit of N-type calcium channel was suggested as the cause of several cases of a myoclonus-dystonia syndrome, although this suggestion has been disputed. Loss-of-function CACNA1B mutations were found to be present in progressive epilepsy-dyskinesia. Clinical significance The alteration of N-type calcium channels in therapeutic processes occurs in four major ways; through the blockage of N-type calcium channel peptides, interference of the flow of ions through the channel itself, activation of G-protein coupled signaling, and interference of the G-protein pathways. Studies have shown that the intrathecal injection of the calcium channel inhibitor ziconotide, to block the N-type calcium channels, have produced alleviation of intractable pain. Blockade of the N-type calcium channel is a potential therapeutic strategy for the treatment of alcoholism. Because prolonged alcohol exposure over time has been known to increase N-type channel function, experiments have shown that using N-type antagonists to decrease channel activity resulted in reduced voluntary consumption of alcohol in mice. Blockers In the pain pathway, N-type calcium channels serve to regulate pain signals sent from the peripheral nervous system to Central Nervous System. Although many N-type calcium channels blockers are known, most potent and selective belong to the family of conotoxins. List of N-type Calcium channel blockers: ω-Conotoxins Cadmium Caroverine Cilnidipine Desipramine Gabapentin nonselectively inhibits N-type calcium channels by attaching to auxiliary α2δ subunit Levetiracetam Lamotrigine Nicardipine NP078585 Piracetam Pregabalin nonselectively inhibits N-type calcium channels by attaching to auxiliary α2δ subunit TROX-1 Ziconotide, a synthetic version of one of conotoxins References Further reading Ion channels Electrophysiology Integral membrane proteins Human proteins Calcium channels