Effects of Ca2+ and other divalent cations on K(+)-evoked force production of slow muscle fibers from Rana esculenta and Rana pipiens.

Slow muscle fibers were dissected from cruralis muscles of Rana esculenta and Rana pipiens. Isometric contractures were evoked by application of K(+)-rich Ringer's containing Ca2+, Ni2+, Co2+, Mn2+ or Mg2+. High (7.2 mmol/liter) external Ca2+ concentration raised, 0 Ca2+ lowered the K+ threshold. Replacing Ca2+ by Ni2+ or Co2+ had an effect similar to that of high Ca2+ Ringer's. In Mg2+ Ringer's the K+ concentration-response curve was flattened. These effects were observed already after short exposure times in both species of slow fibers. When Ca2+ was removed for long periods of time the slow fibers of R. esculenta lost their contractile response to application of high K+ concentrations much more quickly than those of R. pipiens, while the response to caffeine (20 mmol/liter) was maintained. Upon read-mission of Ca2+ contractile ability was quickly restored in the slow fibers of both R. esculenta and R. pipiens, but the effects of Ni2+ (or Co2+, Mn2+ and Mg2+) were much larger in R. esculenta than in R. pipiens slow fibers. It is concluded that divalent cations have two different sites of action in slow muscle fibers. K+ threshold seems to be affected through binding to sites at the membrane surface; these sites bind Ni2+ and Co2+ more firmly than Ca2+. The second site is presumably the voltage sensor in the transverse tubular membrane, which controls force production, and where Ca2+ is the most effective species of the divalent cations examined.