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ATP‐Activated Nonselective Cation Current in NG108‐15 Cells
Author(s) -
Kaiho Hiromi,
Kimura Junko,
Matsuoka Isao,
Kumasaka Tadanori,
Nakanishi Hironori
Publication year - 1996
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1996.67010398.x
Subject(s) - adenosine , chemistry , biophysics , adenosine triphosphate , intracellular , membrane potential , stereochemistry , biochemistry , biology
ATP (1 m M ) induced a biphasic increase in intracellular Ca 2+ concentration ([Ca 2+ ] i ), i.e., an initial transient increase decayed to a level of sustained increase, in NG108‐15 cells. The transient increase was inhibited by a phospholipase C inhibitor, 1‐[6‐[[17β‐3‐methoxyestra‐1,3,5(10)‐trien‐17‐yl]amino]hexyl]‐1 H ‐pyrrole‐2,5‐dione (U73122), whereas the sustained increase was abolished by removal of external Ca 2+ . We examined the mechanism of the ATP‐elicited sustained [Ca 2+ ] i increase using the fura‐2 fluorescent method and the whole‐cell patch clamp technique. ATP (1 m M ) induced a membrane current with the reversal potential of 12.5 ± 0.8 mV (n = 10) in Tyrode external solution. The EC 50 of ATP was ∼0.75 m M . The permeability ratio of various cations carrying this current was Na + (defined as 1) > Li + (0.92 ± 0.01; n = 5) > K + (0.89 ± 0.03; n = 6) > Rb + (0.55 ± 0.02; n = 6) > Cs + (0.51 ± 0.01; n = 5) > Ca 2+ (0.22 ± 0.03; n = 3) > N ‐methyl‐ d ‐glucamine (0.13 ± 0.01; n = 5), suggesting that ATP activated a nonselective cation current. The ATP‐induced current was larger at lower concentrations of external Mg 2+ . ATP analogues that induced the current were 2‐methylthio‐ATP (2MeSATP), benzoylbenzoic‐ATP, adenosine 5′‐thiotriphosphate (ATPγS), and adenosine 5′‐ O ‐(2‐thiodiphosphate), but not adenosine, ADP, α,β‐methylene‐ATP (AMPCPP), β,γ‐methylene‐ATP (AMPPCP), or UTP. Concomitant with the current data, 2MeSATP and ATPγS, but not AMPCPP or AMPPCP, increased the sustained [Ca 2+ ] i increase. We conclude that ATP activates a class of Ca 2+ ‐permeable nonselective cation channels via the P 2z receptor in NG108‐15 cells.