TY - JOUR
T1 - Calcium current and charge movement of mammalian muscle
T2 - action of amyotrophic lateral sclerosis immunoglobulins.
AU - Delbono, O.
AU - García, J.
AU - Appel, Stanley H.
AU - Stefani, E.
N1 - Copyright:
Copyright 2016 Elsevier B.V., All rights reserved.
PY - 1991/12/1
Y1 - 1991/12/1
N2 - 1. The Vaseline-gap voltage clamp technique was used to record dihydropyridine (DHP)-sensitive Ca2+ currents (I(Ca)) and charge movement in single cut fibres from the rat extensor digitorum longus (EDL) muscle. Amyotrophic lateral sclerosis (ALS) immunoglobulin G (IgG) action on I(Ca) and charge movement has been characterized. 2. ALS IgG reduced I(Ca) amplitude. The peak I(Ca) of EDL fibres (mean ± S.E.M.) at 0 m V, expressed as amperes per membrane capacitance, was 4.79 ± 0.029 A F-1, while after 30 min incubation in ALS IgG it was 2.52 ± 0.04 A F-1. IgG from healthy patients, and from patients with other diseases (familial ALS, myasthenia gravis, chronic relapsing inflammatory polyneuritis, multiple sclerosis and one sample from Lambert-Eaton syndrome, LES) did not affect I(Ca), while IgG from patients with Guillain-Barre syndrome and one other sample from a patient with LES affected the I(Ca) in a similar way as ALS IgG. 3. The time constant of I(Ca) activation (α(m)) at 0 m V was 44.8 ± 1.4 ms in control, and 36.6 ± 1.5 ms after an incubation of 30 min in ALS IgG. The steady-state activation curve (m(∞)) was shifted to more positive potentials by ALS IgG. 4. The rate constants of activation (range -20 to 30 mV) were altered by ALS IgG: α(m) decreased while β(m) increased. These data suggest that ALS IgG favours the permanence of the Ca2+ channels in the closed state. 5. The time constant of Ca2+ channels deactivation at -90 mV with a pre-pulse to 0 m V was 4.4 ± 0.5 ms in control and 4.1 ± 0.6 ms in ALS IgG. The relationship between the deactivation time constant and membrane potential was not significantly modified by ALS IgG. 6. I(Ca) inactivation was not affected by ALS IgG. The potentials of half-inactivation were -32.1 and -36. 6 mV in control and ALS IgG, respectively. Similarly, the rate constants of inactivation (α(h) and β(h)) remained unaltered by ALS IgG. 7. The successfully blocked I(Ca) with 100 μM-TMB-8 (3,4,5-trimethoxybenzoic acid 8-(dicthylamino)octyl ester hydrochloride), without major effects on charge movement. We adopted this procedure to study charge movement. ALS IgG reduced charge movement without significant effects on the effective valence and voltage dependence Q(on) and Q(off), the charges during and after the pulse, were similarly affected by ALS IgG. 8. The actions of ALS IgG on DHP-sensitive Ca2+ current and charge movement suggest an interaction between ALS IgG and some component of the DHP-receptor complex.
AB - 1. The Vaseline-gap voltage clamp technique was used to record dihydropyridine (DHP)-sensitive Ca2+ currents (I(Ca)) and charge movement in single cut fibres from the rat extensor digitorum longus (EDL) muscle. Amyotrophic lateral sclerosis (ALS) immunoglobulin G (IgG) action on I(Ca) and charge movement has been characterized. 2. ALS IgG reduced I(Ca) amplitude. The peak I(Ca) of EDL fibres (mean ± S.E.M.) at 0 m V, expressed as amperes per membrane capacitance, was 4.79 ± 0.029 A F-1, while after 30 min incubation in ALS IgG it was 2.52 ± 0.04 A F-1. IgG from healthy patients, and from patients with other diseases (familial ALS, myasthenia gravis, chronic relapsing inflammatory polyneuritis, multiple sclerosis and one sample from Lambert-Eaton syndrome, LES) did not affect I(Ca), while IgG from patients with Guillain-Barre syndrome and one other sample from a patient with LES affected the I(Ca) in a similar way as ALS IgG. 3. The time constant of I(Ca) activation (α(m)) at 0 m V was 44.8 ± 1.4 ms in control, and 36.6 ± 1.5 ms after an incubation of 30 min in ALS IgG. The steady-state activation curve (m(∞)) was shifted to more positive potentials by ALS IgG. 4. The rate constants of activation (range -20 to 30 mV) were altered by ALS IgG: α(m) decreased while β(m) increased. These data suggest that ALS IgG favours the permanence of the Ca2+ channels in the closed state. 5. The time constant of Ca2+ channels deactivation at -90 mV with a pre-pulse to 0 m V was 4.4 ± 0.5 ms in control and 4.1 ± 0.6 ms in ALS IgG. The relationship between the deactivation time constant and membrane potential was not significantly modified by ALS IgG. 6. I(Ca) inactivation was not affected by ALS IgG. The potentials of half-inactivation were -32.1 and -36. 6 mV in control and ALS IgG, respectively. Similarly, the rate constants of inactivation (α(h) and β(h)) remained unaltered by ALS IgG. 7. The successfully blocked I(Ca) with 100 μM-TMB-8 (3,4,5-trimethoxybenzoic acid 8-(dicthylamino)octyl ester hydrochloride), without major effects on charge movement. We adopted this procedure to study charge movement. ALS IgG reduced charge movement without significant effects on the effective valence and voltage dependence Q(on) and Q(off), the charges during and after the pulse, were similarly affected by ALS IgG. 8. The actions of ALS IgG on DHP-sensitive Ca2+ current and charge movement suggest an interaction between ALS IgG and some component of the DHP-receptor complex.
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U2 - 10.1113/jphysiol.1991.sp018903
DO - 10.1113/jphysiol.1991.sp018903
M3 - Article
C2 - 1668354
AN - SCOPUS:0026323792
VL - 444
SP - 723
EP - 742
JO - Journal of Physiology
JF - Journal of Physiology
SN - 0022-3751
IS - 1
ER -