The therapeutic mode of action of 4-aminopyridine in cerebellar ataxia

Journal of Neuroscience

Volumn 30, Issue 21, 2010, Pages 7258-7268

  Alviña, Karina ^a   Khodakhah, Kamran ^a  

^a ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 AMINOPYRIDINE; CHLORZOXAZONE; POTASSIUM CHANNEL KV1.5;

ACCURACY; ACTION POTENTIAL; AFTERHYPERPOLARIZATION; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; ATAXIA; BRAIN CELL; CEREBELLAR ATAXIA; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG EFFICACY; DRUG MECHANISM; EPISODIC ATAXIA TYPE 2; MOUSE; MUTANT; NONHUMAN; PACEMAKER; PRIORITY JOURNAL; PURKINJE CELL; RAT;

4-AMINOPYRIDINE; ACTION POTENTIALS; ANIMALS; ANIMALS, NEWBORN; BEHAVIOR, ANIMAL; CEREBELLAR ATAXIA; CEREBELLUM; CHLORZOXAZONE; CHOREA; DISEASE MODELS, ANIMAL; DOSE-RESPONSE RELATIONSHIP, DRUG; ELECTRIC STIMULATION; EXCITATORY POSTSYNAPTIC POTENTIALS; EXPLORATORY BEHAVIOR; MICE; MICE, INBRED C57BL; MICE, MUTANT STRAINS; PATCH-CLAMP TECHNIQUES; POTASSIUM CHANNEL BLOCKERS; RATS; RATS, WISTAR;

EID: 77953054585     PISSN: 02706474     EISSN: 15292401     Source Type: Journal    
DOI: 10.1523/JNEUROSCI.3582-09.2010     Document Type: Article

References (70)

1. Alvina K, Khodakhah K (2008) Selective regulation of spontaneous activity of neurons of the deep cerebellar nuclei by N-type calcium channels in juvenile rats. J Physiol 586:2523-2538. (Pubitemid 351689810)
2. Ca channels as therapeutic targets in episodic ataxia type-2. J Neurosci 30:7249-7257.
3. Barclay J, Balaguero N, Mione M, Ackerman SL, Letts VA, Brodbeck J, Canti C, Meir A, Page KM, Kusumi K, Perez-Reyes E, Lander ES, Frankel WN, Gardiner RM, Dolphin AC, Rees M (2001) Ducky mouse phenotype of epilepsy and ataxia is associated with mutations in the Cacna2d2 gene and decreased calcium channel current in cerebellar Purkinje cells. J Neurosci 21:6095-6104.
4. Bever CT Jr, Young D, Anderson PA, Krumholz A, Conway K, Leslie J, Eddington N, Plaisance KI, Panitch HS, Dhib-Jalbut S (1994) The effects of 4-aminopyridine in multiple sclerosis patients: results of a randomized, placebo-controlled, double-blind, concentration-controlled, crossover trial. Neurology 44:1054-1059.
5. Buckle PJ, Haas HL (1982) Enhancement of synaptic transmission by 4-aminopyridine in hippocampal slices of the rat. J Physiol 326:109-122. (Pubitemid 12117268)
6. Campbell DB, North JB, Hess EJ (1999) Tottering mouse motor dysfunction is abolished on the Purkinje cell degeneration (pcd) mutant background. Exp Neurol 160:268-278.
7. Cao Y, Dreixler JC, Roizen JD, Roberts MT, Houamed KM (2001) Modulation of recombinant small-conductance Ca(2+)-activated K(+) channels by the muscle relaxant chlorzoxazone and structurally related compounds. J Pharmacol Exp Ther 296:683-689. (Pubitemid 32187335)
8. Capacio BR, Byers CE, Matthews RL, Chang FC (1996) A method for determining 4-aminopyridine in plasma: pharmacokinetics in anaesthetized guinea pigs after intravenous administration. Biomed Chromatogr 10:111-116.
9. Chadderton P, Margrie TW, Hausser M (2004) Integration of quanta in cerebellar granule cells during sensory processing. Nature 428:856-860. (Pubitemid 38529500)
10. Chou R, Peterson K, Helfand M (2004) Comparative efficacy and safety of skeletal muscle relaxants for spasticity and musculoskeletal conditions: a systematic review. J Pain Symptom Manage 28:140-175. (Pubitemid 38970077)
11. Chung YH, Shin C, Kim MJ, Lee BK, Cha CI (2001) Immunohistochemical study on the distribution of six members of the Kv1 channel subunits in the rat cerebellum. Brain Res 895:173-177. (Pubitemid 32231153)
12. Chung YH, Joo KM, Nam RH, Kim YS, Lee WB, Cha CI (2005) Immunohistochemical study on the distribution of the voltage-gated potassium channels in the gerbil cerebellum. Neurosci Lett 374:58-62.
13. Coetzee WA, Amarillo Y, Chiu J, Chow A, Lau D, McCormack T, Moreno H, Nadal MS, Ozaita A, Pountney D, Saganich M, Vega-Saenz dM, Rudy B (1999) Molecular diversity of K+ channels. Ann N Y Acad Sci 868:233-285.
14. Crawley JN (2008) Behavioral phenotyping strategies for mutant mice. Neuron 57:809-818.
15. Davies CH, Pozza MF, Collingridge GL (1993) CGP 55845A: a potent antagonist of GABAB receptors in the CA1 region of rat hippocampus. Neuropharmacology 32:1071-1073.
16. Dove LS, Abbott LC, Griffith WH (1998) Whole-cell and single-channel analysis of P-type calcium currents in cerebellar Purkinje cells of leaner mutant mice. J Neurosci 18:7687-7699.
17. Etzion Y, Grossman Y (2001) Highly 4-aminopyridine sensitive delayed rectifier current modulates the excitability of guinea pig cerebellar Purkinje cells. Exp Brain Res 139:419-425. (Pubitemid 32703948)
18. Evans RM, Zamponi GW (2006) Presynaptic Ca2+ channels - integration centers for neuronal signaling pathways. Trends Neurosci 29:617-624.
19. Fletcher CF, Lutz CM, O'Sullivan TN, Shaughnessy JD Jr, Hawkes R, Frankel WN, Copeland NG, Jenkins NA (1996) Absence epilepsy in tottering mutant mice is associated with calcium channel defects. Cell 87:607-617.
20. Foster KA, Kreitzer AC, Regehr WG (2002) Interaction of postsynaptic receptor saturation with presynaptic mechanisms produces a reliable synapse. Neuron 36:1115-1126.
21. Friedman JH, Hollmann PA (1987) Acetazolamide responsive hereditary paroxysmal ataxia. Mov Disord 2:67-72.
22. Fureman BE, Jinnah HA, Hess EJ (2002) Triggers of paroxysmal dyskinesia in the calcium channel mouse mutant tottering. Pharmacol Biochem Behav 73:631-637.
23. Glasauer S, Kalla R, Buttner U, Strupp M, Brandt T (2005) 4-aminopyridine restores visual ocular motor function in upbeat nystagmus. J Neurol Neurosurg Psychiatry 76:451-453.
24. Grusser-Cornehls U, Baurle J (2001) Mutant mice as a model for cerebellar ataxia. Prog Neurobiol 63:489-540.
25. Harno H, Hirvonen T, Kaunisto MA, Aalto H, Levo H, Isotalo E, Somer H, Kallela M, Palotie A, Wessman M, Farkkila M (2004) Acetazolamide improves neurotological abnormalities in a family with episodic ataxia type 2 (EA-2). J Neurol 251:232-234.
26. Hausser M, Clark BA (1997) Tonic synaptic inhibition modulates neuronal output pattern and spatiotemporal synaptic integration. Neuron 19:665-678.
27. Hayes KC, Katz MA, Devane JG, Hsieh JT, Wolfe DL, Potter PJ, Blight AR (2003) Pharmacokinetics of an immediate-release oral formulation of Fampridine (4-aminopyridine) in normal subjects and patients with spinal cord injury. J Clin Pharmacol 43:379-385.
28. Hoebeek FE, Stahl JS, van Alphen AM, Schonewille M, Luo C, Rutteman M, van den Maagdenberg AM, Molenaar PC, Goossens HH, Frens MA, De Zeeuw CI (2005) Increased noise level of Purkinje cell activities minimizes impact of their modulation during sensorimotor control. Neuron 45:953-965.
29. Hoebeek FE, Khosrovani S, Witter L, De Zeeuw CI (2008) Purkinje cell input to cerebellar nuclei in tottering: ultrastructure and physiology. Cerebellum 7:547-558.
30. Hurlock EC, McMahon A, Joho RH (2008) Purkinje-cell-restricted restoration of Kv3.3 function restores complex spikes and rescues motor coordination in Kcnc3 mutants. J Neurosci 28:4640-4648.
31. Jen J, Kim GW, Baloh RW (2004) Clinical spectrum of episodic ataxia type 2. Neurology 62:17-22. (Pubitemid 38082863)
32. Jen JC, Graves TD, Hess EJ, Hanna MG, Griggs RC, Baloh RW (2007) Primary episodic ataxias: diagnosis, pathogenesis and treatment. Brain 130:2484-2493. (Pubitemid 47511698)
33. Jinnah HA, Hess EJ, LeDoux MS, Sharma N, Baxter MG, DeLongMR (2005) Rodent models for dystonia research: characteristics, evaluation, and utility. Mov Disord 20:283-292. (Pubitemid 40613288)
34. Judge SI, Bever CT Jr (2006) Potassium channel blockers in multiple sclerosis: neuronal Kv channels and effects of symptomatic treatment. Pharmacol Ther 111:224-259.
35. Judge SI, Lee JM, Bever CT Jr, Hoffman PM (2006) Voltage-gated potassium channels in multiple sclerosis: Overview and new implications for treatment of central nervous system inflammation and degeneration. J Rehabil Res Dev 43:111-122.
36. Kalla R, Glasauer S, Buttner U, Brandt T, StruppM (2007) 4-aminopyridine restores vertical and horizontal neural integrator function in downbeat nystagmus. Brain 130:2441-2451. (Pubitemid 47327634)
37. + channels and ultrarapidly activating delayed rectifier potassium current. J Pharmacol Exp Ther 317:1054-1063.
38. Llinas R, SugimoriM (1980) Electrophysiological properties of in vitro Purkinje cell dendrites in mammalian cerebellar slices. J Physiol 305:197-213.
39. Lohle M, Schrempf W, Wolz M, Reichmann H, Storch A (2008) Potassium channel blocker 4-aminopyridine is effective in interictal cerebellar symptoms in episodic ataxia type 2 - a video case report. Mov Disord 23:1314-1316.
40. Madeja M, Musshoff U, Speckmann EJ (1997) Diversity of potassium channels contributing to differences in brain area-specific seizure susceptibility: sensitivity of different potassium channels to the epileptogenic agent pentylenetetrazol. Eur J Neurosci 9:390-395. (Pubitemid 27091117)
41. Maren TH (1967) Carbonic anhydrase: chemistry, physiology, and inhibition. Physiol Rev 47:595-781.
42. Martina M, Yao GL, Bean BP (2003) Properties and functional role of voltage-dependent potassium channels in dendrites of rat cerebellar Purkinje neurons. J Neurosci 23:5698-5707. (Pubitemid 36807848)
43. Matsushita K, Wakamori M, Rhyu IJ, Arii T, Oda S, Mori Y, Imoto K (2002) Bidirectional alterations in cerebellar synaptic transmission of tottering and rolling Ca2+ channel mutant mice. J Neurosci 22:4388-4398.
44. Mori Y, Friedrich T, Kim MS, Mikami A, Nakai J, Ruth P, Bosse E, Hofmann F, Flockerzi V, Furuichi T (1991) Primary structure and functional expression from complementary DNA of a brain calcium channel. Nature 350:398-402.
45. Ophoff RA, Terwindt GM, Vergouwe MN, van Eijk R, Oefner PJ, Hoffman SM, Lamerdin JE, Mohrenweiser HW, Bulman DE, Ferrari M, Haan J, Lindhout D, van Ommen GJ, Hofker MH, Ferrari MD, Frants RR (1996) Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4. Cell 87:543-552.
46. Otis TS, Jen JC (2006) Blessed are the pacemakers. Nat Neurosci 9:297-298.
47. Ovsepian SV, Friel DD (2008) The leaner P/Q-type calcium channel mutation renders cerebellar Purkinje neurons hyper-excitable and eliminates Ca2+-Na+ spike bursts. Eur J Neurosci 27:93-103.
48. Pietrobon D (2005) Function and dysfunction of synaptic calcium channels: insights from mouse models. Curr Opin Neurobiol 15:257-265.
49. Raman IM, Bean BP (1999) Ionic currents underlying spontaneous action potentials in isolated cerebellar Purkinje neurons. J Neurosci 19:1663-1674. (Pubitemid 29094185)
50. Sacco T, Tempia F (2002) A-type potassium currents active at subthreshold potentials in mouse cerebellar Purkinje cells. J Physiol 543:505-520. (Pubitemid 35012205)
51. Shirley TL, Rao LM, Hess EJ, Jinnah HA (2008) Paroxysmal dyskinesias in mice. Mov Disord 23:259-264.
52. Stea A, Tomlinson WJ, Soong TW, Bourinet E, Dubel SJ, Vincent SR, Snutch TP (1994) Localization and functional properties of a rat brain alpha 1A calcium channel reflect similarities to neuronal Q- and P-type channels. Proc Natl Acad Sci U S A 91:10576-10580.
53. Stone TW (1993) Neuropharmacology of quinolinic and kynurenic acids. Pharmacol Rev 45:309-379.
54. Strupp M, Brandt T (2006) Pharmacological advances in the treatment of neuro-otological and eye movement disorders. Curr Opin Neurol 19:33-40. (Pubitemid 43172703)
55. Strupp M, Kalla R, Dichgans M, Freilinger T, Glasauer S, Brandt T (2004) Treatment of episodic ataxia type 2 with the potassium channel blocker 4-aminopyridine. Neurology 62:1623-1625. (Pubitemid 38608211)
56. Strupp M, Kalla R, Freilinger T, Dichgans M, Brandt T (2005) Dysfunction of the brain calcium channel CaV2.1 in absence epilepsy and episodic ataxia-a comment. Brain 128:E32.
57. Strupp M, Zwergal A, Brandt T (2007) Episodic ataxia type 2. Neurotherapeutics 4:267-273.
58. Strupp M, Kalla R, Glasauer S, Wagner J, Hufner K, Jahn K, Brandt T (2008) Aminopyridines for the treatment of cerebellar and ocular motor disorders. Prog Brain Res 171:535-541.
59. Syme CA, Gerlach AC, Singh AK, Devor DC (2000) Pharmacological activation of cloned intermediate- and small-conductance Ca(2+)-activated K(+) channels. Am J Physiol Cell Physiol 278:C570-C581.
60. Usowicz MM, Sugimori M, Cherksey B, Llinas R (1992) P-type calcium channels in the somata and dendrites of adult cerebellar Purkinje cells. Neuron 9:1185-1199. (Pubitemid 23007188)
61. Walter JT, Khodakhah K (2006) The linear computational algorithm of cerebellar Purkinje cells. J Neurosci 26:12861-12872. (Pubitemid 44954606)
62. Walter JT, Alvina K, Womack MD, Chevez C, Khodakhah K (2006) Decreases in the precision of Purkinje cell pacemaking cause cerebellar dysfunction and ataxia. Nat Neurosci 9:389-397. (Pubitemid 43290969)
63. Wan J, Ernstgard L, Song BJ, Shoaf SE (2006) Chlorzoxazone metabolism is increased in fasted Sprague-Dawley rats. J Pharm Pharmacol 58:51-61.
64. Weisz CJ, Raike RS, Soria-Jasso LE, Hess EJ (2005) Potassium channel blockers inhibit the triggers of attacks in the calcium channel mouse mutant tottering. J Neurosci 25:4141-4145.
65. Womack M, Khodakhah K (2002) Active contribution of dendrites to the tonic and trimodal patterns of activity in cerebellar purkinje neurons. J Neurosci 22:10603-10612.
66. Womack MD, Khodakhah K (2003) Somatic and dendritic small-conductance calcium-activated potassium channels regulate the output of cerebellar purkinje neurons. J Neurosci 23:2600-2607.
67. Womack MD, Khodakhah K (2004) Dendritic control of spontaneous bursting in cerebellar Purkinje cells. J Neurosci 24:3511-3521.
68. Womack MD, Chevez C, Khodakhah K (2004) Calcium-activated potassium channels are selectively coupled to P/Q-type calcium channels in cerebellar Purkinje neurons. J Neurosci 24:8818-8822.
69. Yoon KW, Covey DF, Rothman SM (1993) Multiple mechanisms of picrotoxin block of GABA-induced currents in rat hippocampal neurons. J Physiol 464:423-439.
70. Zasorin NL, Baloh RW, Myers LB (1983) Acetazolamide-responsive episodic ataxia syndrome. Neurology 33:1212-1214.