Calcium current activation and charge movement in denervated mammalian skeletal muscle fibres

Abstract

1. Calcium current (ICa) activation was studied in denervated extensor digitorum longus muscle fibres of the rat. Denervation was performed by surgically removing 6-8 mm of the sciatic nerve at the sciatic notch. Controls were normal fibres from non-operated rats. Electrical recordings were carried out using the double Vaseline-gap technique. 2. Current-voltage (I-V) curves showed that the ICa amplitude increased during the first 4-6 days after denervation and subsequently decreased during the second week. Between days 4 and 6 after denervation, the peak ICa amplitude (at 0 mV) was -5.9 +/- 0.5 microA/microF (mean +/- S.E.M.) as compared with -4.8 +/- 0.3 microA/microF in normal fibres. Between days 14 and 15 after denervation, the ICa amplitude was -2.9 +/- 0.4 microA/microF. 3. The time constant of ICa activation (tau a) was significantly increased by denervation. At 0 mV, tau a in normal fibres was 44.8 +/- 1.4 ms. Between 4 and 6 days after denervation tau a was 58.1 +/- 4.8 ms, and between 14 and 15 days after denervation, 55.8 +/- 3.8 ms. 4. The time constant of deactivation (tau d) decreased after denervation. At -10 mV, the tau d in normal fibres was 103.4 +/- 14 ms. The value decreased to 74.5 +/- 8.6 and 74.0 +/- 17 ms between days 4 and 6 and days 14 and 15 of denervation respectively. 5. Charge movement (Qon) was reduced progressively without major changes in the steepness (k) and position on the voltage axis of the Qon-Vm relationship. The fitted parameters under control were Qmax = 15.4 nC/microF, mid-point potential Vq1/2 = -25.2 mV and k = 11.9 mV. Between days 14 and 15 of denervation, the values for Qmax, Vq1/2 and k were 6.7 nC/microF, -36.8 mV and 11.3 mV respectively. 6. Calcium permeability (PCa) in normal and denervated fibres at stages during denervation was calculated according to the Hodgkin-Huxley model. At 0 mV PCa was 1.24 x 10(-5) cm/s in normal fibres, and 7.43 x 10(-6) cm/s after 2 weeks of denervation. 7. The m infinity-Vm relationship was shifted to more positive potentials after denervation without significant changes in the steepness factor k. The V1/2 value in normal fibres was -4.4 mV, and 5.8 mV after two weeks of denervation. 8. The ICa sensitivity to nifedipine was not modified in the different groups of denervated fibres studied. With 10 microM-nifedipine, the 1-(ICa in nifedipine/ICa control) relationships were 0.74 +/- 0.03 in normal fibres and 0.76 +/- 0.12, 14 days after denervation.