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Adenosine inhibits voltage‐dependent Ca 2+ currents in rat dissociated supraoptic neurones via A 1 receptors
Author(s) -
Noguchi Jun,
Yamashita Hiroshi
Publication year - 2000
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2000.00313.x
Subject(s) - adenosine , depolarization , supraoptic nucleus , agonist , pertussis toxin , medicine , adenosine a1 receptor , adenosine receptor , endocrinology , chemistry , biophysics , receptor , patch clamp , adenosine receptor antagonist , inhibitory postsynaptic potential , g protein , biology , biochemistry , oxytocin
1 The modulation of voltage‐dependent Ca 2+ currents ( I Ca ) by adenosine was investigated in magnocellular neurones acutely dissociated from the rat hypothalamic supraoptic nucleus (SON) by using the whole‐cell patch‐clamp technique. 2 Adenosine dose dependently and reversibly inhibited I Ca elicited by depolarizing voltage steps from a holding potential of ‐80 mV to potentials ranging from ‐30 to +20 mV. The mean (± s.e.m.) maximum inhibition rate was 36.1 ± 4.1 % ( n = 6 ) at ‐20 mV and the EC 50 was 9.8 × 10 − 7 M ( n = 6 ). 3 The inhibition of I Ca by adenosine was completely reversed by the selective A 1 receptor antagonist 8‐cyclopentyl theophylline (CPT), and was mimicked by the selective A 1 receptor agonist N 6 ‐cyclohexyladenosine (CHA). 4 The inhibition by CHA was strongly reduced when I Ca was inhibited by ω‐conotoxin GVIA, a blocker of N‐type Ca 2+ channels. 5 The adenosine‐induced inhibition of I Ca was largely reversed by a depolarizing prepulse to +150 mV for 100 ms, which is known to reverse the inhibition of Ca 2+ channels mediated by G‐protein βγ subunits. 6 The adenosine receptor‐mediated inhibition of I Ca was not abolished by intracellularly applied preactivated pertussis toxin (PTX). 7 Using immunohistochemistry, G z α‐like immunoreactivity (a PTX‐resistant inhibitory G‐protein) was observed throughout the SON. 8 These results suggest that adenosine modulates the neuronal activity of SON neurones by inhibiting N‐type voltage‐dependent Ca 2+ channels via A 1 receptors which are coupled to PTX‐resistant G‐proteins.