The relationship between the action potential, intracellular calcium and force in intact phasic, guinea-pig uretic smooth muscle.
1. We investigated the relationship between the action potential, Ca2+ and phasic force in intact guinea-pig ureter, following physiological activation. 2. The action potential elicited a Ca2+ transient consisting of three components: a fast increment, associated with the first action potential spike, a slower increment, associated with subsequent spikes and the initial part of the plateau component, and a steady-state phase associated with the plateau. 3. Prolongation of the plateau, by agonists, prolonged the third component of the Ca2+ transient and increased force amplitude and duration. 4. The force-Ca2+ relationship during phasic contractions showed hysteresis; more force was produced as Ca2+ declined than when it rose. Paired pulse stimuli suggested that the delay between Ca2+ and force was not due to mechanical properties. Wortmannin, which has been shown to selectively inhibit force and myosin light chain (MLC) phosphorylation in the guinea-pig ureter, did not affect electrical activity or Ca2+ but significantly increased the delay, suggesting that myosin phosphorylation is a major contributor to it. 5. Prolongation of the duration of the [Ca2+]i transient, at unchanged amplitude, increased force. The rise of [Ca2+]i did not limit the rate of contraction. Slowing of the rate of [Ca2+]i rise abolished the hysteresis between Ca2+ and force. 6. Cooling reduced force, increased the delay and hysteresis between Ca2+ and force, but did not affect the rate of rise of Ca2+. The reduction in force could be compensated, by increasing the duration of the Ca2+ transient. 7. We suggest that in vivo, steady-state force-Ca2+ relationships are not applicable in phasic smooth muscles. Furthermore, agonists increase force mainly by prolonging the action potential, which increases the duration of the [Ca2+] signal.
Burdyga
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The Physiological Laboratory, The University of Liverpool, Crown Street, Liverpool L69 3BX, UK.
Wray
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D000200:Action Potentials / Q000502:physiology; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003080:Cold Temperature; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism*; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D013696:Temperature; D014513:Ureter / Q000187:drug effects / Q000502:physiology*; D000077191:Wortmannin
D000730:Androstadienes; D002118:Calcium; D000077191:Wortmannin