page_title: N-type calcium channel
section_title: Clinical significance
hierarchical_section_title: N-type calcium channel / Clinical significance
caption_attribution_description: English: Osteoarthritis. This is an edited version of the source image made for use in the "Anatomist" iOS and Android app and shared here under the terms of the source image's Share Alike Creative Commons license.
context_page_description: N-type calcium channels are voltage gated calcium channels that are distributed throughout the entire body. These channels are high voltage activated channels composed of alpha-1B subunits. The alpha subunit forms the pore through which the calcium enters and helps to determine most of the channel's properties. The alpha subunit is also known as the calcium channel/voltage dependent/N type, alpha 1 subunit, or calcium voltage-gated channel subunit alpha1 B. The subunit is essential to modulate neurotransmitter release. They also contain associated subunits such as β1, β3, β4, α2δ, and possibly γ. These channels are known for their importance in the nervous system. They play a small role in the migration of immature neurons before the establishment of their mature synapses, and they are critically involved in the release of neurotransmitters, which is also similar to another type of calcium channels, known as P-type calcium channels. N-type calcium channels are targets for the development of drugs to relieve chronic and neuropathic pain. They are also used for the treatment of hypertension, autism spectrum disorder, osteoarthritis, and other medical diagnoses.
context_section_description: N-type calcium channels have been connected to a variety of different clinical diagnoses. 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. They are most commonly linked to therapeutic treatment of chronic pain. Studies have shown that the intrathecal injection of calcium channel inhibitors such as Ziconotide, to block the N-type calcium channels, have produced alleviation of intractable pain. Administering N-type peptide blockers via injection into the spinal canal (intrathecal injection) allows the drugs to reach the cerebral spinal fluid where the channels are located. The use of blockers to inhibit the N-type calcium channels have produced alleviation of chronic pain from a variety of different diseases. For example, blockade of the N-type calcium channel is a potential therapeutic strategy for the treatment of alcoholism using N-type channel antagonists. Because prolonged alcohol exposure over time has been known to increase N-type channel function, experiments have been performed to determine the effect inhibiting them has on alcohol addiction. Studies have shown that using N-type antagonists to decrease channel activity has shown reduced voluntary consumption of alcohol. 
  Studies have also shown that N-type peptide blockers have been used to relieve pain that results from osteoarthritis, hypertension, diabetic neuropathy. It has also been known to be used to aid in relief of pain associated with cancer and can be used for patients actively battling cancer. Studies are being done to see if the treatment may also be used for those survivors still experiencing chronic pain. Also, due to the N-type calcium channel being intrinsic to neurotransmitter release and excitability, they can be regulated via GPCR signaling using Analgesic opioid drugs to relieve pain. This is done by modulating the sensory transmitter release and subsequently lessening the feelings of pain  and cancer. However, the use of intrathecally injected N-type channel blockers has proven to be more beneficial than common opioid remedies because there are less negative side effects associated.  
  
  The Cav2.2 channel inhibitor, Ziconotide, for example, is the only drug on the market as of now that directly targets the n-type channel and its conotoxin peptide. N-type calcium channels have also been associated with several known diseases as well. For example, mutations in the CACNA1B gene have been associated with Myoclonus-Dystonia syndrome, an unusual hyperkinetic movement disorder with muscular contractile symptoms. This can be explained by the fact that the channel is mutated with an increase in current flow, subsequently causing hyperexcitability. It has also been linked to cardiac arrhythmia, as increased excitability can cause tachycardia. Issues with the alpha subunit of the N-type calcium channel  . Duplication of the CACNA1B gene has also been linked to cases of the autism spectrum disorder as well as psychiatric diseases such as bipolar disorder and schizophrenia.
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caption: Osteoarthritis
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