Differential Effects of Divalent Cations on Nerve and Muscle Membranes

Abstract

Many divalent cations are known to influence biological activities. Among them, calcium is essential to many cellular functions. Elucidation of mechanism of action of these divalent cations may shed light on the molecular basis of cellular activities in the living organisms. In a serial study of effects of nine divalent cations (e. g., U0₂ ²⁺, Cd²⁺, Zn²⁺, Mn²⁺, Co²⁺, Ni²⁺, Cu²⁺, Ba²⁺ and Sr²⁺) on the neuromuscular transmission of the skeletal muscles, we found that these cations exerted different effects on the nerve and muscle transmission process. U02²⁺ was a unique cation capable of increasing acetylcholine release from nerve endings, while Cd²⁺ inhibited the release. Zn²⁺, Mn²⁺, Co²⁺ and Ni²⁺ not only inhibited transmitter release but also depressed muscle membrane functions. Both Cu²⁺ and Ba²⁺ induce muscle contractions prior to the blockade of neuromuscular transmission. We also examined the interaction of these cations with synaptosomes, liposomes and sarcoplasmic reticulum (SRJ of the skeletal muscle. These cations inhibited ⁴⁵Ca²⁺ uptake and (Na⁺+K⁺)-ATPase of synaptosomes, Ca²⁺-ATPase of SR, and phospholipase A₂ and 5’-nucleotidase of Na. ia na. ia atra venom. In general, (Na⁺+K⁺)-ATPase was the most and 5’- nucleotidase was the least sensitive to these cations. UO₂ ²⁺ and Cd²⁺ were most potent in inhibition of Ca²⁺- uptake and (Na⁺+K⁺)-ATPase of synaptosomes. Zn²⁺ markedly inhibited (Na⁺K⁺-ATPase and phospholipase A₂ while Cu²⁺ was rather selective in inhibiting Ca²⁺-ATPase of SR. Mn²⁺ and Ba²⁺ were only moderately or slightly active in depressing these activities. Interaction of these cations (except UO₂ ²⁺) with synaptosomes, SR and liposomes enhanced the fluorescence intensity of 1-anilino-8- naphthalene sulfonate (ANS). Possible interaction of these cations with sulfhydryl or phosphoryl groups of membrane proteins and phospholipids was also explored. A proposed model for the mode of action of these cations on the cell membrane will be presented.