P/Q-type

G0 was isolated as an other PTx-ribosylated G-protein which co-purifies with G, but which does not inhibit adenylate cyclase. There are two main isoforms (G0l and Go2), with additional splice-variants. G0 is particularly abundant in the nervous system, comprising up to 1% of membrane proteins. Its main function is to reduce the opening probability of those voltage-gated Ca2+ channels (N- and P/Q-type) involved in neurotransmitter release. Hence, it is largely responsible for the widespread auto-inhibition of transmitter secretion by presynaptic receptors and this effect is mediated through released py subunits. 

P/Q-type Cav2.1 t lA Neuron presynaptic terminals, heart, brain... 

Perroy, J., Prezeau, L. M. D. W., Shigemoto, R Bockaert, J., and Fagni, L. (2000) Selective blockade of P/Q-type calcium channels by the metabotropic glutamate receptor type 7 involves a phospholipase C pathway in neurons. J. Neurosci. 20,7896-7904. 

Fink K, Meder WP, Clusmann H, Gothert M (2002) Ca2+ entry via P/Q-Type Ca2+ channels and the Na+/Ca2+ exchanger in rat and human neocortical synaptosomes. Naunyn Schmiedebergs Arch Pharmacol 366 458 163... 

Peptides from cone snails and spiders - molecular probes for N- and P/Q- type Ca2+ channels... 

Cypros Pharm. Corp. describes the use of polyguanidino derivatives as presynaptic N- and P/Q-type calcium channel blockers for i.v. (or i.c.v.) administration (Marangos et al. (Cypros Pharmaceutical Corp.), W09836743). Compound 5 was administered to gerbils (7.5 mg/kg i.v.) prior to bilateral carotid occlusion. After 72 h the animals were sacrificed. Brains were perfusion-fixed and sections were stained to enable quantitative cell counts of live and dead neurons. The number of damaged neurons in the subiculum was 91.5 compared to 214 for a control treated with saline. It has been claimed that this compound can be used for the treatment of neuropathic pain and for the protection of neurons from excitatory damage under conditions of cerebral hypoxia. 

Clinical trials with new L- type and especially N - or P/Q -type VDCC inhibitors are eagerly awaited. 

Kazuyuki, M., Kiyomi, K., Yoshitaka, A., Toshiyuki, K. (Shionogi Co.), P/Q type calcium channel antagonist, WO9801121 (1998). 

It has been demonstrated that cannabinoids act to suppress action potential-evoked calcium rises in the presynaptic terminal, thereby decreasing transmitter release. The action potential-evoked rise in intraterminal calcium was decreased by postsynaptic depolarization. This postsynaptic depolarization induced reduction of presynaptic calcium was prevented by application of antagonists to the CBi receptor (Kreitzer and Regehr, 2001). Cannabinoid-induced decreases in synaptic transmission have been shown to result from an inhibition of N- and P/Q-type calcium channels, the subtypes through which calcium influx occurs during evoked transmitter release (Twitchell et al., 1997). 

Twitchell, W., Brown, S., Mackie, K. Cannabinoids inhibit N- and P/Q-type calcium channels in cultured rat hippocampal neurons, J. Neurophysiol. 1997, 78, 43-50. 

Keywords calcium channel, L-type, P/Q-type, T-type, < subunit, 3 subunit, <. C subunit, y subunit,... 

P/Q-TYPE (Cav2.1/a1A) CALCIUM CHANNELS CACNA1A GENE... 

P/Q-type channels with CAG expansion transfected in HEK293 cells results in perinuclear aggregates and cell death (Ishikawa et al., 1999)... 

Figure 1. Mutations in the human Cnv 2.1 (P/Q-type) voltage-gated calcium channel associated with Familial Hemiplegic Migraine (FHM) and Spinocerebellar Ataxia Type-6 (SCA6)...

Additional substantiating evidence that calcium channel auxiliary subunits might play pivotal roles in disease processes comes from the study of mouse models. Five murine diseases with similar phenotypes to Cav2.1 P/Q-type channel mutant-associated diseases have been linked to calcium channel auxiliary subunits (Tables 9-11). 

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