p type calcium channels


Summary: CALCIUM CHANNELS located within the PURKINJE CELLS of the cerebellum. They are involved in stimulation-secretion coupling of neurons.

Top Publications

  1. Fletcher C, Tottene A, Lennon V, Wilson S, Dubel S, Paylor R, et al. Dystonia and cerebellar atrophy in Cacna1a null mice lacking P/Q calcium channel activity. FASEB J. 2001;15:1288-90 pubmed
  2. Kaja S, van de Ven R, van Dijk J, Verschuuren J, Arahata K, Frants R, et al. Severely impaired neuromuscular synaptic transmission causes muscle weakness in the Cacna1a-mutant mouse rolling Nagoya. Eur J Neurosci. 2007;25:2009-20 pubmed
    ..Taken together, our studies indicate that the gait abnormality of RN mice is due to a combination of ataxia and muscle weakness and that RN models aspects of the NMJ dysfunction in LEMS. ..
  3. Xie G, Clapcote S, Nieman B, Tallerico T, Huang Y, Vukobradovic I, et al. Forward genetic screen of mouse reveals dominant missense mutation in the P/Q-type voltage-dependent calcium channel, CACNA1A. Genes Brain Behav. 2007;6:717-27 pubmed
    ..The Wobbly mutant thus highlights the importance of the voltage sensor and provides a starting point to unravel the neuropathological mechanisms of this disease. ..
  4. Matsushita K, Wakamori M, Rhyu I, Arii T, Oda S, Mori Y, et al. Bidirectional alterations in cerebellar synaptic transmission of tottering and rolling Ca2+ channel mutant mice. J Neurosci. 2002;22:4388-98 pubmed
  5. Katoh A, Jindal J, Raymond J. Motor deficits in homozygous and heterozygous p/q-type calcium channel mutants. J Neurophysiol. 2007;97:1280-7 pubmed
    ..Basal VOR and optokinetic reflex performance were normal in the heterozygotes but severely impaired in the leaner and alpha1A knockout homozygotes...
  6. Walter J, Alviña K, Womack M, Chevez C, Khodakhah K. Decreases in the precision of Purkinje cell pacemaking cause cerebellar dysfunction and ataxia. Nat Neurosci. 2006;9:389-97 pubmed
    ..Our data support the hypothesis that the precision of intrinsic pacemaking in Purkinje cells is essential for motor coordination and suggest that K(Ca) channels may constitute a potential therapeutic target in EA2...
  7. Pietrobon D. Calcium channels and channelopathies of the central nervous system. Mol Neurobiol. 2002;25:31-50 pubmed
  8. Sawada K, Sakata Haga H, Ando M, Takeda N, Fukui Y. An increased expression of Ca(2+) channel alpha(1A) subunit immunoreactivity in deep cerebellar neurons of rolling mouse Nagoya. Neurosci Lett. 2001;316:87-90 pubmed
    ..Increased expression of the alpha(1A) subunit in deep cerebellar neurons might compensate for the altered function of the P/Q-type Ca(2+) channel of RMN. ..
  9. Jouvenceau A, Eunson L, Spauschus A, Ramesh V, Zuberi S, Kullmann D, et al. Human epilepsy associated with dysfunction of the brain P/Q-type calcium channel. Lancet. 2001;358:801-7 pubmed
    ..Human absence epilepsy can be associated with dysfunction of the brain P/Q-type voltage-gated Ca(2+) channel. The phenotype in this patient has striking parallels with the mouse absence epilepsy models. ..

More Information


  1. Kaja S, van de Ven R, Broos L, Veldman H, van Dijk J, Verschuuren J, et al. Gene dosage-dependent transmitter release changes at neuromuscular synapses of CACNA1A R192Q knockin mice are non-progressive and do not lead to morphological changes or muscle weakness. Neuroscience. 2005;135:81-95 pubmed
    ..1 channels and show that the resulting altered neurotransmitter release is not associated with morphological changes at the NMJ or muscle weakness, not even in the longer term. ..
  2. van den Maagdenberg A, Pietrobon D, Pizzorusso T, Kaja S, Broos L, Cesetti T, et al. A Cacna1a knockin migraine mouse model with increased susceptibility to cortical spreading depression. Neuron. 2004;41:701-10 pubmed
    ..Our data show that the increased susceptibility for CSD and aura in migraine may be due to cortical hyperexcitability. The R192Q FHM-1 mouse is a promising animal model to study migraine mechanisms and treatments. ..
  3. Hoebeek F, Stahl J, Van Alphen A, Schonewille M, Luo C, Rutteman M, et al. Increased noise level of purkinje cell activities minimizes impact of their modulation during sensorimotor control. Neuron. 2005;45:953-65 pubmed
    ..This study demonstrates the importance of regularity of firing in Purkinje cells for neuronal information processing. ..
  4. Plomp J, Vergouwe M, van den Maagdenberg A, Ferrari M, Frants R, Molenaar P. Abnormal transmitter release at neuromuscular junctions of mice carrying the tottering alpha(1A) Ca(2+) channel mutation. Brain. 2000;123 Pt 3:463-71 pubmed
    ..This study shows that functional consequences of alpha(1A) mutations causing cerebral disorders can be characterized at the NMJ. ..
  5. Wakamori M, Yamazaki K, Matsunodaira H, Teramoto T, Tanaka I, Niidome T, et al. Single tottering mutations responsible for the neuropathic phenotype of the P-type calcium channel. J Biol Chem. 1998;273:34857-67 pubmed
  6. Doyle J, Ren X, Lennon G, Stubbs L. Mutations in the Cacnl1a4 calcium channel gene are associated with seizures, cerebellar degeneration, and ataxia in tottering and leaner mutant mice. Mamm Genome. 1997;8:113-20 pubmed
  7. Zwingman T, Neumann P, Noebels J, Herrup K. Rocker is a new variant of the voltage-dependent calcium channel gene Cacna1a. J Neurosci. 2001;21:1169-78 pubmed
    ..Overall these findings point to an important dissociation between the seizure phenotypes and the abnormalities in catecholamine metabolism, and they emphasize the value of allelic series in the study of gene function. ..
  8. Stahl J, James R, Oommen B, Hoebeek F, De Zeeuw C. Eye movements of the murine P/Q calcium channel mutant tottering, and the impact of aging. J Neurophysiol. 2006;95:1588-607 pubmed
    ..The data suggest at least four pathophysiological mechanisms (two congenital and two acquired) are required to explain the ocular motor deficits in the two Cacna1a mutant strains. ..
  9. Fletcher C, Lutz C, O Sullivan T, Shaughnessy J, Hawkes R, Frankel W, et al. Absence epilepsy in tottering mutant mice is associated with calcium channel defects. Cell. 1996;87:607-17 pubmed
    ..These studies define the first mutations in a mammalian central nervous system-specific voltage-sensitive calcium channel and identify the first gene involved in absence epilepsy. ..
  10. Jun K, Piedras Rentería E, Smith S, Wheeler D, Lee S, Lee T, et al. Ablation of P/Q-type Ca(2+) channel currents, altered synaptic transmission, and progressive ataxia in mice lacking the alpha(1A)-subunit. Proc Natl Acad Sci U S A. 1999;96:15245-50 pubmed
    ..The alpha(1A)(-/-) mice provide a starting point for unraveling neuropathological mechanisms of human diseases generated by mutations in alpha(1A). ..
  11. Lim S, Mason W, Young N, Chen R, Bower J, McKeon A, et al. Polymyoclonus, laryngospasm, and cerebellar ataxia associated with adenocarcinoma and multiple neural cation channel autoantibodies. Arch Neurol. 2009;66:1285-7 pubmed publisher
    ..We highlight the importance of recognizing polymyoclonus. To our knowledge, this is also the first description of a syndrome of polymyoclonus, laryngospasm, and ataxia associated with adenocarcinoma and these cation channel antibodies. ..
  12. Arias Montaño J, Floran B, Floran L, Aceves J, Young J. Dopamine D(1) receptor facilitation of depolarization-induced release of gamma-amino-butyric acid in rat striatum is mediated by the cAMP/PKA pathway and involves P/Q-type calcium channels. Synapse. 2007;61:310-9 pubmed
    ..These observations provide evidence that dopamine D(1) agonist facilitation of the depolarization-induced release of GABA from striatal terminals is mediated by the cAMP/PKA pathway and involves mainly P/Q-type Ca(2+) channels. ..
  13. Currie K, Fox A. Differential facilitation of N- and P/Q-type calcium channels during trains of action potential-like waveforms. J Physiol. 2002;539:419-31 pubmed
    ..Since the ratio of N-type to P/Q-type Ca(2+) channels varies widely between synapses, differential facilitation may contribute to the fine tuning of synaptic transmission, thereby increasing the computational repertoire of neurons. ..
  14. Iegorova O, Fisyunov A, Krishtal O. G-protein-independent modulation of P-type calcium channels by mu-opioids in Purkinje neurons of rat. Neurosci Lett. 2010;480:106-11 pubmed publisher
    ..These observations indicate that mu-type opioid receptors modulate P-type calcium channels in Purkinje neurons via G-protein-independent mechanism. ..
  15. Hogan Q, McCallum J, Sarantopoulos C, Aason M, Mynlieff M, Kwok W, et al. Painful neuropathy decreases membrane calcium current in mammalian primary afferent neurons. Pain. 2000;86:43-53 pubmed
    ..Altered Ca(2+) signalling in injured sensory neurons may contribute to hyperexcitability leading to neuropathic pain. ..
  16. Gazulla J, Tintore M. [P/Q-type voltage-dependent calcium channels in neurological disease]. Neurologia. 2007;22:511-6 pubmed
    ..Research about calcium channelopathies should clarify how altered channel function produces disease and lead to new treatments for these conditions. ..
  17. Li L, Bischofberger J, Jonas P. Differential gating and recruitment of P/Q-, N-, and R-type Ca2+ channels in hippocampal mossy fiber boutons. J Neurosci. 2007;27:13420-9 pubmed
    ..In conclusion, single MFBs coexpress multiple types of Ca2+ channels, which are activated differentially by subthreshold and suprathreshold presynaptic voltage signals. ..
  18. Kim J, Kwak S, Kim D, Won M, Choi H, Song H, et al. Up-regulation of P/Q-type voltage-gated Ca2+ channel immunoreactivity within parvalbumin positive neurons in the rat hippocampus following status epilepticus. Neurosci Res. 2007;57:379-86 pubmed
    ..These findings suggest that SE may induce prolonged up-regulation in P/Q-type VGCC expression within PV positive neurons. ..
  19. Jobling P. omega-Conotoxin-GVIA-sensitive calcium channels on preganglionic nerve terminals in mouse pelvic and celiac ganglia. Auton Neurosci. 2009;146:56-61 pubmed publisher
    ..However, release of ACh from sacral parasympathetic preganglionic neurons requires calcium entry from both N-type and toxin-resistant calcium channels. ..
  20. Yu Y, Maureira C, Liu X, McCormick D. P/Q and N channels control baseline and spike-triggered calcium levels in neocortical axons and synaptic boutons. J Neurosci. 2010;30:11858-69 pubmed publisher
    ..These results demonstrate novel mechanisms by which calcium currents may control the electrophysiological properties of axonal spike generation and neurotransmitter release in the neocortex. ..
  21. Zhu L, Liu D, Hu J, Cheng J, Wang S, Wang Q, et al. GSK-3 beta inhibits presynaptic vesicle exocytosis by phosphorylating P/Q-type calcium channel and interrupting SNARE complex formation. J Neurosci. 2010;30:3624-33 pubmed publisher
    ..These results indicate that GSK-3beta negatively regulates synaptic vesicle fusion events via interfering with Ca(2+)-dependent SNARE complex formation. ..
  22. Cao Y, Tsien R. Effects of familial hemiplegic migraine type 1 mutations on neuronal P/Q-type Ca2+ channel activity and inhibitory synaptic transmission. Proc Natl Acad Sci U S A. 2005;102:2590-5 pubmed
    ..Thus, mutant-expressing synapses might be weakened in a heightened state of neuromodulation like that provoked by triggers of migraine such as stress. ..
  23. Baell J, Duggan P, Forsyth S, Lewis R, Lok Y, Schroeder C. Synthesis and biological evaluation of nonpeptide mimetics of omega-conotoxin GVIA. Bioorg Med Chem. 2004;12:4025-37 pubmed
    ..1 microM) showed a greater than 25-fold selectivity for the N-type channel. ..
  24. Scarborough G. Why we must move on from the E1E2 model for the reaction cycle of the P-type ATPases. J Bioenerg Biomembr. 2003;35:193-201 pubmed
    ..This new model will therefore serve us better as we seek to unravel the final details of the molecular mechanism of active ion transport catalyzed by these enzymes. It is thus time to move on from the traditional E1E2 model. ..
  25. Yan Z, Chi P, Bibb J, Ryan T, Greengard P. Roscovitine: a novel regulator of P/Q-type calcium channels and transmitter release in central neurons. J Physiol. 2002;540:761-70 pubmed
  26. Nahm S, Jung K, Enger M, Griffith W, Abbott L. Differential expression of T-type calcium channels in P/Q-type calcium channel mutant mice with ataxia and absence epilepsy. J Neurobiol. 2005;62:352-60 pubmed
    ..These results suggest that differential expression of T-type calcium channels in the leaner cerebellum may be involved in the observed movement disorders. ..
  27. Guida S, Trettel F, Pagnutti S, Mantuano E, Tottene A, Veneziano L, et al. Complete loss of P/Q calcium channel activity caused by a CACNA1A missense mutation carried by patients with episodic ataxia type 2. Am J Hum Genet. 2001;68:759-64 pubmed
    ..These results indicate that a complete loss of P/Q channel function is the mechanism underlying EA2, whether due to truncating or to missense mutations. ..
  28. Santiago A, Carvalho C, Carvalho A, Ambrósio A. Differential contribution of L-, N-, and P/Q-type calcium channels to [Ca2+]i changes evoked by kainate in hippocampal neurons. Neurochem Res. 2008;33:1501-8 pubmed publisher
    ..The results indicate that hippocampal neurons differ in what concerns their L-, N- and P/Q-type Ca(2+) channels activated by stimulation of the AMPA/kainate receptors. ..
  29. Nagayama S, Koike F, Sakai T, Antoku Y, Yukitake M, Kuroda Y. [Case of anti P/Q type VGCC antibody positive small lung cell carcinoma that occured with subacute cerebellar degeneration, Lambert-Eaton myasthenic syndrome, and brainstem encephalitis]. Brain Nerve. 2008;60:1470-4 pubmed
    ..SCLC also recurred later. We hypothesized that VGCC of the brainstem was damaged by anti-P/Q-type VGCC antibody. ..
  30. Millán C, Sánchez Prieto J. Differential coupling of N- and P/Q-type calcium channels to glutamate exocytosis in the rat cerebral cortex. Neurosci Lett. 2002;330:29-32 pubmed
  31. Hsieh Y, Yang E, Hsu E, Chow Y, Kou R. Voltage-dependent calcium channels in the corpora allata of the adult male loreyi leafworm, Mythimna loreyi. Insect Biochem Mol Biol. 2002;32:547-57 pubmed
    ..loreyi, and that the N-type VDCCs may play important roles in these cellular events. ..
  32. Scholle H, Jinnah H, Arnold D, Biedermann F, Faenger B, Grassme R, et al. Kinematic and electromyographic tools for characterizing movement disorders in mice. Mov Disord. 2010;25:265-74 pubmed publisher
    ..These studies provide insights into how these methods can be used for delineating movement disorders in mice and for how they may be compared with similar disorders of humans. ..
  33. Rodriguez Fermepín M, Alvarez Maubecín V, Zarrabeitía V, Bianciotti L, Vatta M, Fernandez B. Atrial natriuretic factor (ANF) effects on L-, N-, and P/Q-type voltage-operated calcium channels. Cell Mol Neurobiol. 2002;22:771-81 pubmed
    ..Thus, ANF modulates neuronal NE release through different mechanisms involving presynaptic calcium channel inhibition. ..
  34. Minami K, Raymond C, Martin Moutot N, Ohtake A, Van Renterghem C, Takahashi M, et al. Role of Thr(11) in the binding of omega-conotoxin MVIIC to N-type Ca2+ channels. FEBS Lett. 2001;491:127-30 pubmed
    ..Inhibition of Ba2+ current by the analogs did not completely correlate with binding affinity, although binding to BHK cells was comparable to rat cerebellar membranes. ..
  35. Kaja S, van de Ven R, Ferrari M, Frants R, van den Maagdenberg A, Plomp J. Compensatory contribution of Cav2.3 channels to acetylcholine release at the neuromuscular junction of tottering mice. J Neurophysiol. 2006;95:2698-704 pubmed
    ..This is the first report of compensatory expression of non-Cav2.1 channels at NMJs of mice with a single amino acid change in Cav2.1. ..
  36. Khavandgar S, Walter J, Sageser K, Khodakhah K. Kv1 channels selectively prevent dendritic hyperexcitability in rat Purkinje cells. J Physiol. 2005;569:545-57 pubmed
    ..Further, we show that Kv1 channels also contribute to dendritic integration of parallel fibre synaptic input. Kv1 channels are often targeted to soma and axon and the data presented support a major dendritic function for these channels. ..
  37. Takahashil E, Nagasu T. Genetic background influences P/Q-type Ca2+ channel alpha1A subunit mRNA expression in olfactory bulb and reproductive ability of N-type Ca2+ channel alpha1B subunit-deficient mice. Biochem Genet. 2005;43:287-98 pubmed
    ..These results suggest that the genetic background influences alpha1A subunit mRNA expression and reproductive ability in alpha1B-deficient mice. ..
  38. Orecna M, Hafko R, Toporcerová V, Strbak V, Bacova Z. Cell swelling-induced insulin secretion from INS-1E cells is inhibited by extracellular Ca2+ and is tetanus toxin resistant. Cell Physiol Biochem. 2010;26:197-208 pubmed publisher
    ..Hypotonicity-induced insulin secretion from INS-1E cells is inhibited by extracellular Ca(2+), does not require intracellular Ca(2+) and is TeTx resistant. ..
  39. Iwanami M, Odaka M, Nakamura T, Hirata K. [Paraneoplastic cerebellar degeneration and Lambert-Eaton myasthenic syndrome associated with anti P/Q-type voltage-gated calcium channel antibody in a patient with primary double lung cancer]. Brain Nerve. 2009;61:1083-7 pubmed
    ..Physicians need to be aware that patients may develop PCD and LEMS associated with anti-VGCC antibody caused by small cell lung cancer, and a mass survey should be conducted and careful examinations performed...
  40. Luisi R, Panza E, Barrese V, Iannotti F, Viggiano D, Secondo A, et al. Activation of pre-synaptic M-type K+ channels inhibits [3H]D-aspartate release by reducing Ca2+ entry through P/Q-type voltage-gated Ca2+ channels. J Neurochem. 2009;109:168-81 pubmed publisher
  41. Molenaar P. A relative weak leg muscle in the rolling Nagoya mouse as a model for Lambert-Eaton myasthenic syndrome. J Neuroimmunol. 2008;201-202:166-71 pubmed publisher
    ..The results suggest that leg weakness in LEMS may result from a relatively small safety factor of neuromuscular transmission and that this could become particularly prominent when the activity of calcium channels is diminished. ..
  42. Takahashi E, Kajiwara N, Furuya K, Sugiyama F, Yagami K. Expression analysis of the 5'-upstream region of mouse P/Q-type Ca(2+) channel alpha( lA) subunit gene fused to Escherichia coli lacZ reporter gene in the spinal cord using transgenic mice. Neurosci Lett. 2000;284:9-12 pubmed
    ..3-kb 5'-upstream region alone is not sufficient for the expression. ..
  43. Adams P, Snutch T. Calcium channelopathies: voltage-gated calcium channels. Subcell Biochem. 2007;45:215-51 pubmed
    ..At least in those instances wherein the channelopathies can be attributed to gain-of-function mechanisms, the data point towards new therapeutic strategies for developing highly selective calcium channel antagonists...
  44. French L, Lanning C, Harris Warrick R. The localization of two voltage-gated calcium channels in the pyloric network of the lobster stomatogastric ganglion. Neuroscience. 2002;112:217-32 pubmed
  45. Jeng C, Sun M, Chen Y, Tang C. Dominant-negative effects of episodic ataxia type 2 mutations involve disruption of membrane trafficking of human P/Q-type Ca2+ channels. J Cell Physiol. 2008;214:422-33 pubmed
    ..Taken together, our data suggest that EA2 mutants induce significant ER retention of their wild-type counterparts, thereby suppressing the functional expression of Ca(V)2.1 channels. ..
  46. Martín R, Torres M, Sánchez Prieto J. mGluR7 inhibits glutamate release through a PKC-independent decrease in the activity of P/Q-type Ca2+ channels and by diminishing cAMP in hippocampal nerve terminals. Eur J Neurosci. 2007;26:312-22 pubmed
    ..Thus, mGluR7 mediates the inhibition of glutamate release at hippocampal nerve terminals primarily by inhibiting P/Q-type Ca(2+) channels, although augmenting the levels of cAMP reveals the ability of the receptor to decrease cAMP. ..
  47. Perroy J, El Far O, Bertaso F, Pin J, Betz H, Bockaert J, et al. PICK1 is required for the control of synaptic transmission by the metabotropic glutamate receptor 7. EMBO J. 2002;21:2990-9 pubmed
    ..These results indicate that the scaffolding protein, PICK1, plays an essential role in the control of synaptic transmission by the mGlu7a receptor complex. ..
  48. Kang M, Felix R, Campbell K. Long-term regulation of voltage-gated Ca(2+) channels by gabapentin. FEBS Lett. 2002;528:177-82 pubmed
  49. Millán C, Lujan R, Shigemoto R, Sánchez Prieto J. Subtype-specific expression of group III metabotropic glutamate receptors and Ca2+ channels in single nerve terminals. J Biol Chem. 2002;277:47796-803 pubmed
    ..This specific coexpression of different group III mGluRs and Ca(2+) channels may endow synaptic terminals with distinct release properties and reveals the existence of a high degree of presynaptic heterogeneity. ..
  50. Kim D, Kwak S, Kim J, Kim J, Won M, Kang T. The selective effects of somatostatin- and GABA-mediated transmissions on voltage gated Ca2+ channel immunoreactivity in the gerbil hippocampus. Brain Res. 2006;1115:200-8 pubmed
    ..These findings also suggest that up-regulated VGCC immunoreactivity may be consequence of the neuronal excitability caused by a reduction in inhibitory neurotransmission in the gerbil hippocampus. ..
  51. Urbano F, Piedras Rentería E, Jun K, Shin H, Uchitel O, Tsien R. Altered properties of quantal neurotransmitter release at endplates of mice lacking P/Q-type Ca2+ channels. Proc Natl Acad Sci U S A. 2003;100:3491-6 pubmed
    ..Changes in presynaptic function were also associated with a significant reduction in the size of postsynaptic acetylcholine receptor clusters. ..
  52. Takamori M. What's in the serum of seronegative MG and LEMS?. Neurology. 2003;61:277; author reply 277-8 pubmed
  53. Dobrev D, Ravens U. Therapeutically relevant concentrations of neomycin selectively inhibit P-type Ca2+ channels in rat striatum. Eur J Pharmacol. 2003;461:105-11 pubmed
    ..In conclusion, therapeutically relevant concentrations of neomycin preferentially block P-type Ca(2+) channels which regulate dopamine release in rat striatum. This block could be responsible for aminoglycoside-induced toxicity. ..