The mode of action of local anesthetics on the calcium pump of brain.
Subcellular vesicles present in brain microsomal fraction take up calcium by an ATP-dependent process which is probably one of the mechanisms involved in the regulation of free calcium ions concentratioon in the cytosol of nerve cells. The experiments described in this paper were designed to test the effect of local anesthetics on this transport system since it is known that cytoplasmic calcium concentration interferes with nerve excitability and conduction and transmitter release. It was found that tetracaine increases the rate of calcium uptake in the range of 0.5 to 3 mM and inhibits calcium uptake in the range of 4 to 7 mM. Lidocaine and procaine increase calcium uptake in the range of 5 to 30 mM and inhibit calcium uptake in the range of 40 to 70 mM. The effects of local anesthetics were also tested on th ATP hydrolysis coupled with calcium uptake and on the ATP in equilibrium Pi exchange which represents the reverse reaction of this transport system. It was found that three local anesthetics inhibit ATP in equilibrium Pi exchange in concentrations which increase calcium uptake and inhibit ATP hydrolysis in concentrations which inhibit calcium uptake. These findings indicate that the enhancement of calcium uptake by the lower concentrations of local anesthetics is due to a decrease of the reverse reaction, whereas inhibition of calcium uptake by the higher concentrations of local anesthetics is due to the blockage of the transport adenosine triphosphatase.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D006868:Hydrolysis; D066298:In Vitro Techniques; D008861:Microsomes / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism; D011817:Rabbits
D000779:Anesthetics, Local; D010710:Phosphates; D000255:Adenosine Triphosphate; D002118:Calcium