Proceedings of The Physiological Society

Puerto de la Cruz, Tenerife (2003) J Physiol 548P, O13

Oral Communications

Role of PKC in control of force-Ca2+ relationship in phasic ureteric smooth muscle

S. Shabir and T. Burdyga

Physiological Laboratories, University of Liverpool, Crown Street, Liverpool L69 3BX, UK


Many agonists work through a PKC pathway, and so its modulation on the force-Ca2+ relationship in phasic ureter smooth muscle has been investigated.

Female Wistar rats and Duncan Hartley guinea-pigs were anaesthetised using CO2, and killed by cervical dislocation. The ureters were loaded with indo-1-AM, and force and calcium measured. Data are given as means ± S.E.M., and n is the number of animals.

In the guinea-pig ureter both carbachol (n = 3) and a PKC activator (0.1 µM PdBu, n = 4) increased the amplitude of the phasic contractions evoked by electrical stimulations (carbachol, 60 ± 7% PdBu, 70 ± 29 %). This was associated mainly with an increase in the duration of the Ca2+ transient (carbachol, 22 % ± 2% PdBu, 38 ± 6 %). The selective inhibitor of PKC, 5 µM GF109203X reversed the stimulant action of PdBu, and partially reduced the stimulatory action of carbachol. The effects of carbachol and PdBu on the amplitude of the phasic contractions and duration of the calcium transient were not additive.

In rat ureter, carbachol (n = 3) and PdBu (n = 3) also increased the amplitude of phasic contractions (24 ± 8 % and 31 ± 5 %, respectively) but also markedly slowed the relaxation of the phasic contractions. The calcium transients however were not significantly affected by either agent suggesting force is being mainly affected by a change in sensitivity of the contractile machinery to calcium. The effects of PdBu on the amplitude and relaxation rate were completely reversed by the PKC inhibitor GF109203X, while that of carbachol was only partially reversed.

These data suggest that in ureter the effects of agonists on phasic contractions are species dependent. In the guinea-pig ureter agonists increase the amplitude of force, mainly by increasing the duration of the Ca2+ transient. We now show that part of this effect could be mediated by activation of PKC, which can increase the duration of the calcium transient via a prolongation of the action potential (Burdyga & Wray, 1999). In the rat ureter, agonists stimulate force mainly via sensitisation of the contractile machinery to Ca by activation of PKC and Rho/ROK pathways, as shown previously (Shabir & Burdyga, 2002).

We would like to thank the MRC for their funding.

Where applicable, experiments conform with Society ethical requirements