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Proc Natl Acad Sci U S A. Dec 15, 1993; 90(24): 11743–11747.
PMCID: PMC48060

IgG from amyotrophic lateral sclerosis patients increases current through P-type calcium channels in mammalian cerebellar Purkinje cells and in isolated channel protein in lipid bilayer.

Abstract

The effect of the IgG from amyotrophic lateral sclerosis (ALS) patients was tested on the voltage-dependent barium currents (IBa) in mammalian dissociated Purkinje cells and in isolated P-type calcium channels in lipid bilayers. Whole cell clamp of Purkinje cells demonstrates that ALS IgG increases the amplitude of IBa without modifying their voltage kinetics. This increased IBa could be blocked by a purified nonpeptide toxin from Agelenopsis aperta venom (purified funnel-web spider toxin) or by a synthetic polyamine analog (synthetic funnel-web spider toxin) and by a peptide toxin from the same spider venom, omega-Aga-IVA. Similar results were obtained on single-channel recordings from purified P channel protein. The addition of ALS IgG increased single-channel IBa open time without affecting slope conductance. The results described above were not seen with normal human IgG nor with boiled ALS IgG. It is concluded that ALS IgG enhances inward current through P-type calcium channels. Since P-type Ca2+ channels are present in motoneuron axon terminals, we propose that the enhanced calcium current triggered by ALS IgG may contribute to neuronal damage in ALS.

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  • Delbono O, García J, Appel SH, Stefani E. IgG from amyotrophic lateral sclerosis affects tubular calcium channels of skeletal muscle. Am J Physiol. 1991 Jun;260(6 Pt 1):C1347–C1351. [PubMed]
  • Magnelli V, Sawada T, Delbono O, Smith RG, Appel SH, Stefani E. The action of amyotrophic lateral sclerosis immunoglobulins on mammalian single skeletal muscle Ca2+ channels. J Physiol. 1993 Feb;461:103–118. [PMC free article] [PubMed]
  • Appel SH, Engelhardt JI, García J, Stefani E. Immunoglobulins from animal models of motor neuron disease and from human amyotrophic lateral sclerosis patients passively transfer physiological abnormalities to the neuromuscular junction. Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):647–651. [PMC free article] [PubMed]
  • Uchitel OD, Protti DA, Sanchez V, Cherksey BD, Sugimori M, Llinás R. P-type voltage-dependent calcium channel mediates presynaptic calcium influx and transmitter release in mammalian synapses. Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3330–3333. [PMC free article] [PubMed]
  • Regan LJ, Sah DW, Bean BP. Ca2+ channels in rat central and peripheral neurons: high-threshold current resistant to dihydropyridine blockers and omega-conotoxin. Neuron. 1991 Feb;6(2):269–280. [PubMed]
  • Llinás R, Sugimori M, Hillman DE, Cherksey B. Distribution and functional significance of the P-type, voltage-dependent Ca2+ channels in the mammalian central nervous system. Trends Neurosci. 1992 Sep;15(9):351–355. [PubMed]
  • Llinás RR, Sugimori M, Cherksey B. Voltage-dependent calcium conductances in mammalian neurons. The P channel. Ann N Y Acad Sci. 1989;560:103–111. [PubMed]
  • Cherksey BD, Sugimori M, Llinás RR. Properties of calcium channels isolated with spider toxin, FTX. Ann N Y Acad Sci. 1991;635:80–89. [PubMed]
  • Kay AR, Wong RK. Isolation of neurons suitable for patch-clamping from adult mammalian central nervous systems. J Neurosci Methods. 1986 May;16(3):227–238. [PubMed]
  • Llinás R, Sugimori M. Electrophysiological properties of in vitro Purkinje cell somata in mammalian cerebellar slices. J Physiol. 1980 Aug;305:171–195. [PMC free article] [PubMed]
  • Usowicz MM, Sugimori M, Cherksey B, Llinás R. P-type calcium channels in the somata and dendrites of adult cerebellar Purkinje cells. Neuron. 1992 Dec;9(6):1185–1199. [PubMed]
  • Mintz IM, Venema VJ, Swiderek KM, Lee TD, Bean BP, Adams ME. P-type calcium channels blocked by the spider toxin omega-Aga-IVA. Nature. 1992 Feb 27;355(6363):827–829. [PubMed]
  • Nowycky MC, Fox AP, Tsien RW. Three types of neuronal calcium channel with different calcium agonist sensitivity. Nature. 1985 Aug 1;316(6027):440–443. [PubMed]
  • Racker E, Knowles AF, Eytan E. Resolution and reconstitution of ion-transport systems. Ann N Y Acad Sci. 1975 Dec 30;264:17–33. [PubMed]
  • Coronado R, Latorre R. Phospholipid bilayers made from monolayers on patch-clamp pipettes. Biophys J. 1983 Aug;43(2):231–236. [PMC free article] [PubMed]
  • Smith RG, Hamilton S, Hofmann F, Schneider T, Nastainczyk W, Birnbaumer L, Stefani E, Appel SH. Serum antibodies to L-type calcium channels in patients with amyotrophic lateral sclerosis. N Engl J Med. 1992 Dec 10;327(24):1721–1728. [PubMed]
  • Lin JW, Rudy B, Llinás R. Funnel-web spider venom and a toxin fraction block calcium current expressed from rat brain mRNA in Xenopus oocytes. Proc Natl Acad Sci U S A. 1990 Jun;87(12):4538–4542. [PMC free article] [PubMed]
  • Hillman D, Chen S, Aung TT, Cherksey B, Sugimori M, Llinás RR. Localization of P-type calcium channels in the central nervous system. Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7076–7080. [PMC free article] [PubMed]

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