GABAA receptor modulation by protein tyrosine kinase in the rat diagonal band of Broca

The diagonal band of Broca (DBB) is involved in a wide array of physiological functions which are, in part, mediated by activation of GABA(A) receptors. DBB is enriched in GABA and protein tyrosine kinase (PTK) immunoreactivity. Whole-cell patch-clamp recording were performed from acutely dissociated DBB neurons to investigate the involvement of PTK in GABA(A) receptor function. The activation of GABA(A) receptor by the selective agonist, muscimol (5 mu M) was dependent on the presence of intracellular ATP. Omission of ATP in the intracellular medium resulted in a fast decrement of the response whereas inclusion of sodium orthovanadate (100 mu M), a non-specific phosphatase inhibitor, augmented the response and inhibited 'run down' of the response. Genistein (100 mu M) and tyrphostin B-44 (-), specific inhibitors of PTK, attenuated the response to muscimol. The muscimol response was not affected by daidzein (100 mu M; an inactive analogue of genistein) nor by tetraethylammonium bromide (1 mM). These observations suggest that phosphorylation is important for the activation and long term maintenance of GABA(A) receptor function. PTK phosphorylation, which has been previously identified as an important event in signal transduction, may modulate GABA mediated neurotransmission in the forebrain. (C) 1997 Elsevier Science B.V.