The inhibitory effect of lithium on high-K induced contraction in guinea-pig taenia coli

Summary

• 1. This study deals with the effects of lithium (Li) on the membrane potential, tension development, intracellular Na, K and Li contents and ⁴⁵Ca uptake of smooth muscle of the guinea-pig taenia coli depolarized by high-K (62.7 mM) solution.

• 2. Replacement of Na with Li in high-K solution resulted in a concentration-dependent inhibition of muscle contraction without affecting membrane depolarization. The effect of Li-substitution was also dependent on the duration of exposure to Li and was antagonized by raising the concentration of external Ca ([Ca]₀). Replacement of Na with tris (hydroxymethyl) aminomethane (Tris), sucrose or choline did not show such an inhibitory effect.

• 3. To estimate the intracellular Na content by removing extracellular bound Na, muscle strips were washed with cold Li solution and the amount of Na remaining in the tissue was measured. During washout with the cold Li-solution, a part of the tissue Na was rapidly lost followed by a rapid Li uptake while the remaining Na was lost very slowly as a single exponential process. A similar change in tissue Li level was observed in Li-loaded tissue during washout with cold Na-solution. The residual Na and Li after a 1 h washout with the cold solutions were regarded as intracellular Na and Li, respectively.

• 4. Replacement of a part of the extracellular Na in high-K solution with either Li or sucrose led to a slight decrease in intracellular Na. In the case of Li substitution, Li gradually accumulated in the muscle cells. The increase in intracellular Li was dependent on the concentration of external Li.

• 5. The relaxation produced by Li was correlated with the intracellular Li content of the tissues. Both the Li-induced relaxation and the increased intracellular Li were fully reversible with similar time courses following removal of extracellular Li.

• 6. ⁴⁵Ca uptake of the muscle measured by a modified “La-method” increased in high-K solution. This increase was inhibited by a pretreatment with Li.

• 7. It is suggested that the action of Li is closely related to an accumulation of intracellular Li, which may produce muscle relaxation mainly by inhibiting the depolarization-induced Ca influx.