Protein kinase C mediates P2U purinergic receptor inhibition of K+ channel in apical membrane of strial marginal cells

Differential expression of P2Y receptors in the rat cochlea during development

“…The movement of K + out of the stria vascularis and into the endolymph is important to regulation of endolymph potassium concentration and the positive endocochlear potential. The KCNE1 subunit has a protein kinase C regulatory domain which can be activated via the P2Y 4 receptor-PLC b -diacylglycerol (DAG)-protein kinase C (PKC) pathway [11]. As we confirmed in the present study, P2Y 4 co-localizes on the apical membrane of the strial marginal cells with KCNE1, whereas P2Y 2 is localized in a separate, basal cell layer of this specialized ion transport epithelium [29].…”

“…As noted, the stria vascularis is the only tissue facing the endolymphatic compartment that does not express P2X receptor/ATP-gated ion channels. Studies by Marcus et al [11,29,42] have revealed that the marginal cells of the stria vascularis provide a conductance pathway for K + flux into scala media via KCNQ1/KCNE1 ion channels. The movement of K + out of the stria vascularis and into the endolymph is important to regulation of endolymph potassium concentration and the positive endocochlear potential.…”

“…This tissue is also a source of vesiculated ATP in the marginal cells which is likely to contribute to the elevation of ATP within this cochlear fluid compartment during noise stress [9,10]. ATP release would activate P2Y receptors on the marginal cells, resulting in reduction in the K + conductance of these cells (paracrine action) [11]. Along with activation of P2X receptors, this mechanism contributes to a reduction in endocochlear potential [12].…”

“…P2Y 12 , P2Y 13 , and P2Y 14 receptor signal transduction utilizes G ia -mediated inhibition of adenylate cyclase and hence reduction in cAMP (reviewed by [14,15]). Endogenous P2Y receptor signaling may also engage additional pathways, including stimulation of adenylate cyclase (P2Y 11 ), and activation of phospholipase D, phospholipase A2, MEK/MAP kinase, and Rhodependent kinase (for ERK signaling) [15]. The P2Y-PLC pathway may also mediate Ca 2+ entry through transient receptor potential (TRP) channels, gated by membranebound diacylglycerol (DAG) [16,17].…”

“…The P2Y-PLC pathway may also mediate Ca 2+ entry through transient receptor potential (TRP) channels, gated by membranebound diacylglycerol (DAG) [16,17]. In broad terms, P2Y 1 and P2Y 11 are ATP preferring [14]; P2Y 12 and P2Y 13 are ADP preferring [14]; rat P2Y 2 and P2Y 4 orthologs are equally activated by ATP and UTP [18] and P2Y 6 is preferentially activated by UDP, with ADP > ATP [19]; P2Y 14 is activated most potently by UDP-glucose [14]. However, the functional significance of the agonist preferences of the P2Y receptors needs to be matched to the endogenous ligand environment.…”