Membrane-restricted regulation of Ca²⁺ release and influx in polarized epithelia

Abstract

EPITHELIAL cells exist in a complex setting in which responses to mucosal or serosal environments are mediated by receptors expressed on specialized cellular domains, such as apical versus basolateral cell membranes. We investigated whether airway epithelia can react selectively through G-protein-coupled receptors to stimuli in the mucosal or serosal environments by measuring inositol phosphate and intracellular Ca²⁺ responses in polarized human nasal epithelial monolayers. We report here that unilateral ATP (10^á¤-4 M) administration stimulated P₂ purinoceptors and tapped pools of intracellular Ca²⁺ associated with the plasma membrane ipsilateral but not contralateral to stimulated receptors. Similarly, activation of plasma membrane Ca²⁺ influx by ATP was confined to the membrane ipsilateral to receptor stimulation. These findings demonstrate that polarized epithelia restrict P₂ receptor-mediated responses to a single domain of the cell, reflecting membrane-specific generation and catabolism of inositol phosphates and confinement of calcium influx regulation to the membrane ipsilateral to the stimulated receptors.