Coordinated Regulation of Shrinkage-induced Na/H Exchange and Swelling-induced [K-C1] Cotransport in Dog Red Cells Further Evidence from Activation Kinetics and Phosphatase Inhibition

Hypertonic shrinkage of dog red cells caused rapid activation of Na/H exchange and rapid deactivation of [K-C1] cotransport. Hypotonic swelling caused delayed deactivation of Na/H exchange and delayed activation of [K-CI] cotransport. Okadaic acid stimulated shrinkage-induced Na/H exchange and inhibited swelling-induced [K-C1] cotransport. The data are compatible with the kinetic model of Jennings and AI-Rohil (1990. J. Gen. Physiol. 95:1021-1040) for volume regulation of [K-C1] cotransport in rabbit red cells and suggest that in dog red cells Na/H exchange and [K-C1] cotransport are controlled by a common regulatory system. The proposal of Jennings and Schulz (1991. J. Gen. Physiol. 96:799-817) that activation/deactivation of volume-sensitive transport involves phosphorylation/ dephosphorylation of a regulatory protein is supported by these observations. I N T R O D U C T I O N Na/H exchange and [K-C1] cotransport can be reversibly activated and deactivated in dog red cells. In a previous report we presented evidence that these two systems are reciprocally linked, so that when one is turned on, the other is turned off. For example, activation of Na/H exchange and suppression of [K-C1] cotransport occur when cells are shrunken, or when they are loaded with Mg or Li ions. Conversely, suppression of Na/H exchange and activation of [K-CI] cotransport occur when cells are swollen, depleted of Mg ions, or hemolyzed and resealed (Parker, McManus, Starke, and Gitelman, 1990). The reciprocal behavior of these two transport systems suggests that they are controlled by a separate entity or system that acts as a Address reprint requests to Dr. John C. Parker, Department of Medicine, UNC-Chapel Hill, CB #7035, Chapel Hill, NC 27599-7035. J. GEN. PHYSIOL. © The Rockefeller University Press • 0022-1295/91/11/0869/12 $2.00 Volume 98 November 1991 869-880 869 on M ay 4, 2017 D ow nladed fom Published November 1, 1991