Effects of noradrenaline on the GABA response in rat isolated spiral ganglion neurons in culture.
In the present study, the modulatory effects of noradrenaline (NA) on the GABA response were investigated in the isolated cultured spiral ganglion neurons of rat by using nystatin perforated patch recording configuration under voltage-clamp conditions. NA reversibly depressed GABA response in a concentration-dependent manner and neither changed the reversal potential of the GABA response nor affected the apparent affinity of GABA to its receptor. alpha2-adrenoceptor agonist and antagonist, clonidine and yohimbine mimicked and blocked the NA action on the GABA response, respectively. N-[2(methylamino)ethyl]-5-isoquinoline sulfonamide dihydrochloride (H-89), a protein kinase A inhibitor, mimicked the effect of NA on the GABA response. NA failed to affect the GABA response in the presence of both cAMP and protein kinase A modulator. However, NA still depressed the GABA response even in the presence of both phorbol-12-myristate-13-acetate, a protein kinase C activator and chelerythrine, a protein kinase C inhibitor. These results suggest that the NA suppression of the GABA response is mediated by alpha2-adrenoceptor which reduces intracellular cAMP formation through the inhibition of adenylyl cyclase. Therefore, NA input to the spiral ganglion neurons may modulate the auditory transmission by affecting the GABA response.
Zha
Ding-Jun
DJ
Department of Otorhinolaryngology, Affiliated Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
Wang
Zhi-Ming
ZM
Lin
Ying
Y
Liu
Tao
T
Qiao
Li
L
Lu
Lian-Jun
LJ
Li
Yun-Qing
YQ
Qiu
Jian-Hua
JH
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D020536:Enzyme Activators / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013136:Spiral Ganglion / Q000166:cytology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D020536:Enzyme Activators; D018755:GABA Agonists; D018756:GABA Antagonists; D047428:Protein Kinase Inhibitors; D005680:gamma-Aminobutyric Acid; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D009638:Norepinephrine