Effects of the calcium antagonist nifedipine on the afferent impulse activity of isolated cat muscle spindles.

摘要

The impulse activity of muscle spindles isolated from the cat tenuissimus muscle was investigated under varying concentrations of the L-type calcium channel blocker nifedipine. At a concentration of 25 &mgr;M nifedipine impulse activity was clearly diminished in both primary and secondary endings. However, low concentrations of the drug (5-10 &mgr;M) exerted unexpected excitatory effects. The dynamic properties of primary endings in particular were augmented; those of secondary endings were also increased, although only slightly. A detailed analysis of the afferent discharge patterns obtained under ramp-and-hold stretches yielded the following effects of 10 &mgr;M nifedipine. (1) The initial burst at the beginning of the ramp phase of a stretch was increased in primary endings; (2) the peak dynamic discharge frequency at the end of the ramp phase was considerably increased in most primary endings; (3) the sensitivity of the peak dynamic discharge value to varying amplitudes and velocities of stretch was significantly enhanced in primary endings, and also increased, although only slightly, in secondary endings; (4) the rise in the discharge frequency during the ramp phase of a stretch was augmented in both types of ending, the effect being again stronger in primary endings; (5) the fast adaptive decay of the impulse frequency following the ramp phase of a ramp-and-hold stretch was significantly increased in primary endings, but remained unaffected in secondary endings. The enhanced dynamic properties of primary endings were also observed under small sinusoidal stretch stimuli (10 &mgr;m, 40 Hz), where nifedipine induced a significant shift in the position of the 1:1 driven action potentials toward smaller phase values. In view of an increase in tension in the isolated muscle spindle and an increased initial burst in primary endings in the presence of nifedipine, it is suggested that the drug facilitates the attachment of cross-bridges in the poles of the intrafusal muscle fibers. The increase in the dynamic properties of primary endings points to the possibility that the drug preferentially affects the nuclear bag(1) fiber. The inhibitory effect on the afferent discharge rate at high doses of the drug is interpreted as the consequence of a calcium channel block in the membranes of the sensory endings. The membrane potential of sensory endings appears to be highly dependent on sustained Ca(2+) conductance.