P-type calcium channel
[3] They were able to use an in vitro preparation to examine the ionic currents that account for Purkinje cells' electrophysiological properties.
They found that there are calcium dependent action potentials which rise slowly and fall quickly then undergo hyperpolarization.
Without calcium flux in the Purkinje cells, action potentials fire sporadically at a high frequency.
They are found at axon terminals, as well as in somatodendritic areas of neurons within the central and peripheral nervous system.
[1] P-type calcium channels are also critical to vesicle release, specifically neurotransmitters and hormones[4] at synaptic terminals of excitatory and inhibitory synapses.
[6] The α1 subunit is encoded specifically by the CACNA1A gene[1] and is composed of four domains, each containing six transmembrane (S1-S6) spanning α helices.
[1] The two known blockers which are specific to P-type calcium channels are peptides derived from the spider venom of Agelenopsis aperta.
One advantage of low molecular weight channel blockers is that they can penetrate tissue, which is important for crossing the blood–brain barrier.
Some of these calcium antagonists include verapamil, diltiazem, amlodipine, benidipine, cilnidipine, nicardipine, and barnidipine.
Compounds such as levetiracetam, lamotrigine, and carbamazepine are known to block the P-type channels, which have helped to decrease the occurrence of seizures.
Overall, there are various non-selective calcium channel blockers that help alleviate symptoms of hypertension, schizophrenia, cardiac arrhythmia, epilepsy, pain, asthma, bradycardia, angina pectoris and Alzheimer's disease.
When the calcium current is increased, neurotransmitter release also rises, offering a possible cause for the toxicity in Alzheimer's disease patients.
[5][10] P2X3 receptors are present in trigeminal ganglion neurons[5] and are believed to be a main contributor to familial hemiplegic migraine.
The increased intracellular calcium concentration may contribute to the acute trigeminal pain that typically results in a headache.
[5] Evidence supports that migraines are a disorder of brain excitability characterized by deficient regulation of the cortical excitatory–inhibitory balance.
Levetiracetam inhibits P/Q channel-mediated glutamate release and decreases the excitatory post synaptic currents of both AMPA and NMDA receptors in the hippocampus, specifically the dentate gyrus, which is known to propagate seizure activities.
The inhibition of glutamate release results in an anti-epileptic response in patients because it decreases the excitatory postsynaptic current.
[6] One example of a P-type calcium channel channelopathy is shown in homozygous ataxic mice, who are recessive for both the tottering and leaner genes.
[6] Mutations in the pore forming subunit of P type calcium channels cause ataxia, severely altered respiration, by decreasing minute ventilation and producing symptoms associated with atelectasis.
Mutations to CaV2.1 have also been shown to affect transmission within the pre-Bötzinger Complex, a cluster of interneurons in the brainstem which help to regulate breathing.
