Tachyphylaxis to the Inhibitory Effect of Manganese on Potassium-Induced Contractions in the Isolated Vas Deferens of the Guinea Pig

Abstract

In the isolated vas deferens of the guinea pig, the inhibitory effects of manganese (Mn²⁺) on the contractions induced by potassium (K⁺) were decreased when the contractions were induced repeatedly in the presence of Mn²⁺. This phenomenon appeared to be tachyphylaxis to the inhibitory effects of Mn²⁺. After the repetitive application of K⁺ with Mn²⁺, the phasic component of K⁺-induced contraction was restored, while the tonic component of this contraction and resting tone were augmented by the deprivation of extracellular Mn²⁺. When Mn²⁺ was applied during the tonic component of the K⁺ -induced contraction, the phasic component of the next contraction induced by K⁺ in the absence of Mn²⁺ was slightly inhibited and the tonic component of the contraction was potentiated. When extracellular calcium concentration was increased, the inhibitory effect of Mn²⁺ on K⁺-induced contractions was reduced, while the tachyphylaxis to Mn²⁺ also appeared. Under this condition, the resting tone was markedly increased when the K⁺-induced contraction was repeated in the presence of Mn²⁺. In the calcium-free medium containing Mn²⁺, although K⁺ caused slow and monophasic contractions, the magnitude of the contractions was much smaller than that of the contractions induced in the normal medium containing Mn²⁺. These results suggest that the tachyphylaxis was not produced by the decrement of the inhibitory effects of Mn²⁺ on the contractions but by the augmenting effects of intracellularly accumulated Mn²⁺ and that these augmenting effects of Mn²⁺ are not due to the direct action on the contractile proteins but due to the indirect action of Mn²⁺ which increased the availability of Ca²⁺.