Calcium channels P/Q-type

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. 

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. 

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. 

Adams PJ, Garcia E, Mulatz K, Spacey SD, Snutch TP (2006) Familial Hemiplegic Migraine Mutation K1336E Differentially Affects Calcium-Dependent Facilitation Of P/Q-Type Calcium Channel Splice Variants. FENS Forum Abstracts vol. 3 A084.082. 

Ayata C, Shimizu-Sasamata M, Lo EH, Noebels JL, Moskowitz MA (2000) Impaired neurotransmitter release and elevated threshold for cortical spreading depression in mice with mutations in the alphalA subunit of P/Q type calcium channels. Neuroscience 95 639-645. 

Barrett CF, Cao YQ, Tsien RW (2005) Gating deficiency in a familial hemiplegic migraine type 1 mutant P/Q-type calcium channel. J Biol Chem 280 24064-24071. 

Jouvenceau A, Eunson LH, Spauschus A, Ramesh V, Zuberi SM, Kullmann DM, Hanna MG (2001) Human epilepsy associated with dysfunction of the brain P/Q-type calcium channel. Lancet 358 801-807. 

Knight YE, Bartsch T, Goadsby PJ (2003) Trigeminal antinociception induced by bicuculline in the periaqueductal gray (PAG) is not affected by PAG P/Q-type calcium channel blockade in rat. Neurosci Lett 336 113-116. 

Restituito S, Thompson RM, Eliet J, Raike RS, Riedl M, Chamet P, Gomez CM (2000) The polyglutamine expansion in spinocerebellar ataxia type 6 causes a beta subunit-specific enhanced activation of P/Q-type calcium channels in Xenopus oocytes. J Neurosci 20 6394—6403. 

Spacey SD, Hildebrand ME, Materek LA, Bird TD, Snutch TP (2004) Functional implications of a novel EA2 mutation in the P/Q-type calcium channel. Ann Neurol 56 213-220. 

Sutton KG, McRory JE, Guthrie H, Murphy TH, Snutch TP (1999) P/Q-type calcium channels mediate the activity-dependent feedback of syntaxin-lA. Nature 401 800-804. 

Genistein (42) was found to affect many other types of channels, but the main proposed mechanism of these interactions was indirect. In most cases a PTK pathway was suggested as a putative explanation of the observed effects. Since genistein (42) is a well-known inhibitor of this kinase, we will not focus on those papers and only a short list will be presented. Such a mechanism was mentioned in the case of inhibition of ATP-sensitive K+ channels [325], cardiac slowly activating delayed-rectifier K+ current [326], L-type calcium channels [327,328] (contrary to the direct interaction proposed by Chiang et al. [306] and Yokoshiki et al. [307]), P/Q-type calcium channels in rat hippocampal neurons [329], and carotid baroreceptor activity [330]. A PTK-dependent mechanism was also proposed as the explanation of potentiation of neuronal a7 nAGhRs by genistein (42) [331]. 

Calcium Channelopathies Involving P/Q-Type Calcium Channel ai Subunits. 53... 

It is well established that activation of G protein-coupled receptors (GPCRs), in particular those that couple to the Got / subunit, can result in potent inhibition of both N-type and P/Q-type calcium channels (Figure 2) (Beech et al. 1992 Bemheim et al. 1991 Caulfield et al. 1994 Dunlap and Fischbach 1981 Golardand Siegelbaum 1993 Ikeda 1992 Ikeda and Schofield 1989 Lipscombe et al. 1989 Mintz and Bean 1993 Shapiro and Hille 1993 Zhu and Ikeda 1993). The physio-... 

The activity of N-type and P/Q-type calcium channels is also regulated by proteins that form part of the synaptic vesicle release machinery (Figure 3). These channel subtypes contain a specific synaptic protein interaction site (termed synprint) in the... 

Caulfield MP, Jones S, Vallis Y, Buckley NJ, Kim GD, Milligan G, Brown DA (1994) Muscarinic M-current inhibition via G alpha q/11 and alpha-adrenoceptor inhibition of Ca2+ current via G alpha o in rat sympathetic neurones. J Physiol 477 Pt 3 415-22 Charvin N, L Eveque C, Walker D, Berton F, Raymond C, KataokaM, Shoji-Kasai Y, Takahashi M, De Waard M, Seagar MJ (1997) Direct interaction of the calcium sensor protein synaptotagmin I with a cytoplasmic domain of the alphal A subunit of the P/Q-type calcium channel. Embo J 16 4591-6... 

Lee A, Wong ST, Gallagher D, Li B, Storm DR, Scheuer T, Catterall WA (1999a) Ca2+/calmodulin binds to and modulates P/Q-type calcium channels. Nature 399 155-9 Lee JH, Daud AN, Cribbs LL, Lacerda AE, Pereverzev A, Klockner U, Schneider T, Perez-Reyes E (1999b) Cloning and expression of a novel member of the low voltage-activated T-type calcium channel family. J Neurosci 19 1912-21... 

Martin-Moutot N, Charvin N, Leveque C, Sato K, Nishiki T, Kozaki S, Takahashi M, Seagar M (1996) Interaction of SNARE complexes with P/Q-type calcium channels in rat cerebellar synaptosomes. J Biol Chem 271 6567-70... 

Mochida S, Westenbroek RE, Yokoyama CT, Zhong H, Myers SJ, Scheuer T, Itoh K, CatteraU WA (2003) Requirement for the synaptic protein interaction site for reconstitution of synaptic transmission by P/Q-type calcium channels. Proc Natl Acad Sci U S A 100 2819-24... 

Sutton KG, McRory JE, Guthrie H, Murphy TH, Snutch TP (1999) P/Q-type calcium channels mediate the activity-dependent feedback of syntaxin-lA. Nature 401 800-4 Swartz KJ (1993) Modulation of Ca2+ channels by protein kinase C in rat central and peripheral neurons disruption of G protein-mediated inhibition. Neuron 11 305-20 Swartz KJ, Merritt A, Bean BP, Lovinger DM (1993) Protein kinase C modulates glutamate receptor inhibition of Ca2+ channels and synaptic transmission. Nature 361 165-8 Takahashi SX, Miriyala J, Colecraft HM (2004) Membrane-associated guanylate kinase-like properties of beta-subunits required for modulation of voltage-dependent Ca2+ channels. Proc Natl Acad Sd US A 101 7193-8... 

D2-like receptors couple mainly to Gi/o proteins, as mentioned above. However, there is no direct evidence to support this coupling for the release-modulating autoreceptors. Moreover, the subsequent intracellular signal transduction has never been studied directly in axon terminals. Mouse AtT-20 pituitary cells, which release acetylcholine and adrenocorticotropic hormone, have been used as a model for axon terminals. When expressed in these cells, D3 receptors mediated inhibition of P/Q-type calcium channels and activation of G protein-coupled inward rectifier potassium channels (Kuzhikandathil et al. 1998 Kuzhikandathil and Oxford 1999). Both would explain the autoreceptor-mediated inhibition of dopamine exocytosis. 

Koyama M, Heerdt PM, Levi R (2003) Increased severity of reperfusion arrhythmias in mouse hearts lacking histamine H3-receptors. Biochem Biophys Res Commun 306 792-6 Koyama S, Brodie MS, Appel SB (2007) Ethanol inhibition of M-current and ethanol-induced direct excitation of ventral tegmental area dopamine neurons. J Neurophysiol 97 1977-85 Kuzhikandathil EV, Yu W, Oxford GS (1998) Human dopamine D3 and D2l receptors couple to inward rectifier potassium channels in mammalian cell lines. Mol Cell Neurosci 12 390 102 Kuzhikandathil EV, Oxford GS (1999) Activation of human D3 dopamine receptor inhibits P/Q-type calcium channels and secretory activity in AtT-20 cells. J Neurosci 19 1698-1707... 

Bayliss DA, Li YW, Talley EM. Effects of serotonin on caudal raphe neurons Inhibition of N- and P/Q-type calcium channels and the afterhyperpolarization. J Neurophysiol 1997 77 1362-1374. 

Graus F, Lang B, Pozo-Rosich P, Saiz A, Casamitjana R, Vincent A. P/Q type calcium-channel antibodies in paraneoplastic cerebellar degeneration with lung cancer. Neurology 2002 59(5) 764-766. 

Fukuda T, Motomura M, Nakao Y, Shiraishi H, Yoshimura T, Iwanaga K, et al. Reduction of P/Q-type calcium channels in the postmortem cerebellum of paraneoplastic cerebellar degeneration with Lambert-Eaton myasthenic syndrome. Ann Neurol 2003 53(1) 21-28. 

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