Capsaicin-sensitive stretch responses in ferret trachealis muscle.
1. Stretch-induced electrical and mechanical responses in segments of ferret trachealis muscle were studied. Stretches and post-stretch length changes were quantified by measuring distances between two marker spheres placed on the muscle surface. Electrical responses were determined by measuring membrane potential in the muscle cell syncytium. 2. Smooth muscle mechanical and electrical responses to the stretch manoeuvre were characterized by an initial shortening and depolarization phase and a reversal-repolarization phase. Both phases were resistant to atropine and tetrodotoxin. During the initial phase, the membrane depolarized to potentials as low as -20 mV. For stretches to 1.0 Lmax, from a holding length of 0.75 Lmax, 50% repolarization occurred at 6.8 +/- 0.4 min post-stretch; 50% reversal of shortening of the stretched segment occurred at 6.9 +/- 0.8 min post-stretch. 3. Depolarizing currents generated within muscle cells in the stretched segment spread into cells in non-stretched muscle. Space constants in the transverse and longitudinal directions averaged 480 +/- 46 and 146 +/- 50 microns, respectively. 4. During infusion of capsaicin (10 microM), muscle cells depolarized by 5.5 +/- 2.3 mV. Maximal depolarization was achieved after 15-20 min. After inhibition of neutral enkephalinase, capsaicin-evoked depolarization occurred more rapidly. Muscles depolarized by 11.2 +/- 2.1 mV after about 10 min of capsaicin and then slowly repolarized during continued treatment. When muscle segments were stretched during administration of capsaicin, the initial phase was similar to that observed before capsaicin, but the reversal-repolarization phase was prolonged. Following wash exposure to capsaicin, maximal stretch-induced depolarization was unchanged, but the time for 50% repolarization (t50-repolarization) decreased from the pre-capsaicin value of 8.4 +/- 1.3 to 4.1 +/- 0.5 min. The t50-reversal of stretch-evoked muscle shortening decreased to 54% of control values. 5. Short exposures (< 2 min) to substance P (SP, 1-7.5 microM) depolarized smooth muscle cells. Maximal depolarization was delayed, and occurred after [SP] had decreased to < 10 nM. Repolarization was delayed as long as 6 min following wash-out of SP. Stretches performed when SP-induced depolarization had nearly reversed showed no changes in the initial mechanical or electrical responses, but t50-repolarization increased to 162% of control values. 6. Immunochemical studies showed networks of neurones which react with SP antibodies. 7. These findings suggest that stretch induces SP release from capsaicin-sensitive C fibres, and that released SP affects smooth muscle ionic mechanisms which control and delay the reversal of stretch-induced membrane depolarization and shortening.
Coburn
R F
RF
Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia.
Mitchell
H
H
Dey
R D
RD
Alkon
J
J
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology*; D005260:Female; D005289:Ferrets; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology*; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology; D013314:Stress, Mechanical; D013373:Substance P / Q000494:pharmacology / Q000502:physiology; D015244:Thiorphan / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects* / Q000502:physiology*
D013373:Substance P; D015244:Thiorphan; D002211:Capsaicin