Modulation of nicotinic ACh‐, GABA A ‐ and 5‐HT 3 ‐receptor functions by external H‐7, a protein kinase inhibitor, in rat sensory neurones

1 The effects of external H‐7, a potent protein kinase inhibitor, on the responses mediated by γ‐aminobutyric acid A type (GABA A )‐, nicotinic acetylcholine (nicotinic ACh)‐, ionotropic 5‐hydroxytryptamine (5‐HT 3 )‐, adenosine 5′‐triphosphate (ATP)‐, N‐methyl‐ D ‐aspartate (NMDA)‐ and kainate (KA)‐receptors were studied in freshly dissociated rat dorsal root ganglion neurone by use of whole cell patch‐clamp technique. 2 External H‐7 (1–1000 μ M ) produced a reversible, dose‐dependent inhibition of whole cell currents activated by GABA, ACh and 5‐HT. 3 Whole‐cell currents evoked by ATP, 2‐methylthio‐ATP, NMDA and KA were insensitive to external H‐7. 4 External H‐7 shifted the dose‐response curve of GABA‐activated currents downward without changing the EC 50 significantly (from 15.0±4.0 μ M to 18.0±5.0 μ M ). The maximum response to GABA was depressed by 34.0±5.3%. This inhibitory action of H‐7 was voltage‐independent. 5 Intracellular application of H‐7 (20 μ M ), cyclic AMP (1 m M ) and BAPTA (10 m M ) could not reverse the H‐7 inhibition of GABA‐activated currents. 6 The results suggest that external H‐7 selectively and allosterically modulates the functions of GABA A ‐, nicotine ACh‐ and 5‐HT 3 receptors via a common conserved site in the external domain of these receptors.British Journal of Pharmacology (1997) 122 , 1195–1201; doi: 10.1038/sj.bjp.0701462