In decerebrated rabbits, electrical stimulation of the sural nerve at 1 Hz and intensities of ²ge³ 5 times threshold (T) activates reflexes in the ipsilateral medial gastrocnemius (MG) muscle nerve that show marked temporal summation. When sural C-fibres are activated, the summation shows differential sensitivity to blockade of glutamate N-methyl-D-aspartate (NMDA) receptors, such that summation of Aδ- and C-fibre-evoked reflexes is reduced, but that seen in Aβ-evoked reflexes is not (Clarke et al. 2002). In some preparations, spinal cord neurones show an intrinsic ability to give increasing responses to fixed stimuli that is mediated via L-type calcium channels (Russo & Hounsgaard, 1996). We have investigated the possibility that these channels might be responsible for the non-NMDA-mediated components of temporal summation in the sural-MG reflex.
Experiments were performed in ten rabbits decerebrated under nitrous oxide/halothane (2Ð4 %) anaesthesia. The sural nerve was electrically stimulated with 0.2 ms pulses at strengths of 5.3 T (maximal for the activation of Aβ axons), 15 T (maximal for Aδ afferents), and 92 T (maximal for C fibres). Stimulus cycles consisted of three trains of eight stimuli at 1 Hz, applied successively at Aβ, Aδ and C strengths, and were repeated once per 20 min. Animals were treated intrathecally (I.TH.) with the selective L-type calcium channel antagonist methoxyverapamil at cumulative doses of 0.03, 0.3 and 1 mg, allowing 40 min between each dose. Responses to the final control cycle and the first cycle after each drug dose were analysed for temporal summation, which was quantified by linear regression. Reflex responses were recorded from the ipsilateral MG nerve and integrated in three time bands: 5-12 ms (phase 1), 12Ð100 ms (phase 2) and 100-250 ms (phase 3). Experiments were terminated by intravenous injection of KCl.
In the control state with C-fibre strength stimulation, the slopes (± S.E.M.) of regression lines of reflex size against stimulus number were 40 ± 9, 124 ± 33 and 148 ± 29 mV ms stimulus-1 for phase 1, 2 and 3 reflexes, respectively. Methoxyverapamil (0.3 mg) significantly (t test, P < 0.05) reduced these values to 17 ± 5, 40 ± 5 and 43 ± 14 mV ms stimulus-1, respectively, without having any effect on the size of the responses to the first stimulus in each train (paired t test, P > 0.2). Similar effects were seen when Aδ strength stimuli were used to activate reflexes. The data are thus consistent with the involvement of L-type calcium channels in mediating temporal summation of MG responses to sural nerve input.
This work was supported by BBSRC.
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