Role of ATP and Na⁺ in the Regulation of Cytosolic Free Calcium in Kidney Cells

Abstract

Cytosolic free calcium (Ca_i ²⁺) is controlled by several calcium transporters located at the plasma membrane, the inner membrane of the mitochondria and in the endoplasmic reticulum. Fig. 1 shows the various ATP-dependent pumps and antiporters involved in the control of Ca_i ²⁺ and Na_i ⁺ (In this figure, the plasmalemmal Na⁺-Ca²⁺ antiporter is conventionally assumed to operate in the forward mode i.e. Ca²⁺ efflux energized by Na⁺ influx). Since Ca²⁺ transport out of the cell can be energized by ATP or by the Na⁺ electrochemical potential ΔμNa⁺, a fall in cellular ATP or a drop in ΔμNa⁺ would be expected to depress Ca²⁺ efflux, raise Ca_i ²⁺ and increase the cell Ca²⁺ content. In recent experiments (1,2) performed with cultured monkey kidney cells (LLC-MK₂), my collaborators Dr. K.W. Snowdowne, C.C. Freudenrich and I found that only one of these three predictions was proved correct.