Lithium ion alters Ins(1,4,5)P3 production and mobilisation of intracellular free calcium in k-agonist stimulated rat ventricular myocytes

The effect of lithium ion on the generation of inositol phosphates and the mobilisation of intracellular free calcium in isolated adult rat ventricular myocytes stimulated with k-agonist was studied. Dynorphin1-13 stimulated an increase in the levels of Inositol 1,4,5-trisphosphate (InsP3) and intracellular free calcium ([Ca2+ ]i). Preincubation of the ventricular myocytes with lOmM Li+ for 20 minutes prior to stimulation by dynorphin1-13 reduce the increase of both InsP3 and [Ca2+]i. This effect of Li+ was not seen if 5mM inositol was also present during preincubation. It is concluded that (1) the inhibition of the k-agonist stimulated increase in InsP3 and [Ca2+]i, in Li+-pretreated ventricular myocytes was a result of a depletion of intracellular inositol, due probably to the inhibition by Li+ of inositol monophosphatase which participates in the recycling of intracellular inositol, and (2) the k-agonist induced increase in [Ca2+]i is a consequence of the production of InsP3 since altering the kinetics of production of this compound also altered [Ca2+]i.published_or_final_versio