Differential activation of cation channels and non-selective pores by macrophage P2z purinergic receptors expressed in Xenopus oocytes.

摘要: In macrophages and certain other cell types, extracellular ATP4- can increase plasma membrane permeability through activation of the P2z purinergic receptor. This change involves induction non-selective pores which are permeable to molecules with M(r) < or = 900. Electrophysiological studies indicate that agonist occupation receptors additionally activate cation channels may be distinct from pores. We have observed mammalian expressed in Xenopus oocytes injected mRNA BAC1.2F5 murine macrophage line. Under voltage-clamp analysis, these exhibit a multiphasic inward current response ATP 3'-O-(4-benzoyl)-benzoyl-ATP (BzATP), selective for ATP/BzATP-induced is characterized by rapidly activated phase followed delayed, but steady, conductance. used two-electrode analysis ion substitution further characterize receptor-induced currents as mRNA-injected oocytes. N,N-Hexamethylene amiloride (HMA), potent inhibitor various exchangers channels, selectively reversibly inhibited delayed component BzATP-induced current. HMA-sensitive carried large organic cations, such N-methyl-D-glucamine (NMG+) Tris+, addition small inorganic cations including Na+, Li+, K+. contrast, HMA-insensitive readily K+, poorly NMG+ Tris+. Additional receptor regulation Ca2+ influx, depolarization, ethidium uptake, fura-2 loss native macrophages. Reduced temperature permitted discrimination two pathways could BzATP. At 20 degrees C, BzATP did not significantly (M(r) 195), ethidium+ 314), 831) stimulate an conducting pathway competitively permeated Na+ Ca2+. 37 treatment increased NMG+, ethidium+, fura-2, These data differentially coupled to: 1) gated channel, 2) time- temperature-dependent formation distinguished their rates activation, selectivities, sensitivities analogs, dependence.