Rubidium-87 magnetic resonance spectroscopy and imaging for analysis of mammalian K+ transport

Abstract

This review summarizes results 87Rb MRS/I studies of K+ transport in mammalian cells, organs and in vivo. It provides a brief description of K+ transport systems, their interactions with Rb+ and evidence that Rb+ is a best K+ congener. 87Rb MR studies have focused mostly on isolated perfused rat and pig hearts and to a lesser extent on kidney, skeletal muscle, salivary gland and red blood cells. The method has been used for three purposes: measurements of kinetics of unidirectional Rb+ uptake and efflux and steady-state Rb+ levels. In cardiovascular studies Rb+ has been used in the absence of shift reagent taking advantage of the predominantly intracellular Rb+/K+ distribution (approximately 20:1). Pharmacological analysis of Rb+ uptake and efflux allowed assessment of the contributions of various transporters to the total Rb+ fluxes in rat hearts. It was confirmed that Na+/K+ ATPase is responsible for the majority of K+ influx since Rb+ uptake is 80% ouabain-sensitive and dependent on the intracellular [Na+]. Energy deprivation caused by low-flow ischemia or metabolic inhibition reduced Rb+ uptake rate. Under normal conditions, Rb+ efflux is mediated mainly by voltage-gated K+ channels with a small contribution from the K+/Na+/2Cl- cotransporter. Intracellular alkalosis and osmotic swelling stimulated Rb+ efflux by activation of the putative K+/H+ antiporter. Activity of ATP-sensitive K+ (K(ATP)) channels was revealed by metabolic (2,4-dinitrophenol, ischemia) or pharmacological (K(ATP) opener, P-1075) stimulation of Rb+ efflux, which was reversed by the K(ATP) blocker, glibenclamide. Mitochondrial K+ transport was evaluated in hearts with saponin-permeabilized myocytes and under hypothermic conditions.Three-dimensional (3-D) spectroscopic MRI of isolated beating pig hearts has been used to obtain time series of Rb+ maps of normal and ischemic/infarcted hearts, which showed lower image intensity in the damaged area. Kinetics of Rb+ uptake in the ischemic areas depended on both regional flow and metabolism. The adrenergic agonist dobutamine stimulated Rb+ uptake in normal areas and did not affect uptake in ischemic areas. Drugs that may affect passive Rb+ transport (bumetanide, pinacidil, glibenclamide) did not change Rb+ uptake either in the normal or ischemic zones. 87Rb-MRI was also able to localize ischemia and infarction in blood-perfused hearts. 87Rb MRS/I is an excellent non-invasive research tool for studies of K+ transport in isolated organs and in vivo.