Effect of dinitrophenol and anoxia on isometric tension in rabbit colon smooth muscle.

In a previous study, it was suggested that inhibition of oxidative phosphorylation in smooth muscle is accompanied by a release of Ca2+ from mitochondria (Pettersson 1983); in this investigation, the effects of 2,4-dinitrophenol (DNP) and anoxia on isometric tension in pieces of smooth muscle from rabbit colon were studied. Addition of DNP to the bathing medium elicited a transient and dose-dependent contraction with an ED50 value of 2 X 10(-4) M. The contraction was not inhibited by pretreatment with atropine (1 X 10(-6) M). The removal of external Ca2+ did not reduce the contracting action of DNP. Addition of the local anaesthetic D-mepivacaine (1 X 10(-3) M), which reduces the Ca2+ efflux through the plasma membrane of the smooth muscle cells, augmented the response to DNP. Gassing the bathing medium with 95% N2 + 5% CO2 (anoxia) for 60 min. did not affect the basal tension, but markedly reduced the contractile response to DNP. The results indicate that DNP increased cytoplasmic Ca2+ significantly enough to induce a contraction of rabbit colon smooth muscle by a large release from an intracellular store, probably from the mitochondria. Since anoxia did not mimic the contracting action of DNP, it is suggested that a high concentration of DNP would be a more effective stimulus for mitochondrial Ca2+ release than anoxia.