TY - JOUR
T1 - Adrenergic facilitation of GABAergic transmission in rat entorhinal cortex
AU - Lei, Saobo
AU - Deng, Pan Yue
AU - Porter, James E.
AU - Shin, Hee Sup
PY - 2007/11
Y1 - 2007/11
N2 - Whereas the entorhinal cortex (EC) receives noradrenergic innervations from the locus coeruleus of the pons and expresses adrenergic receptors, the function of norepinephrine (NE) in the EC is still elusive. We examined the effects of NE on GABAA receptor-mediated synaptic transmission in the superficial layers of the EC. Application of NE dose-dependently increased the frequency and amplitude of spontaneous inhibitory postsynaptic currents (IPSCs) recorded from the principal neurons in layer II/III through activation of α1 adrenergic receptors. NE increased the frequency and not the amplitude of miniature IPSCs (mIPSCs) recorded in the presence of TTX, suggesting that NE increases presynaptic GABA release with no effects on postsynaptic GABAA receptors. Application of Ca2+ channel blockers (Cd2+ and Ni2+), omission of Ca2+ in the extracellular solution, or replacement of extracellular Na+ with N-methyl-D-glucamine (NMDG) failed to alter NE-induced increase in mIPSC frequency, suggesting that Ca2+ influx through voltage-gated Ca 2+ or other cationic channels is not required. Application of BAPTA-AM, thapsigargin, and ryanodine did not change NE-induced increase in mIPSC frequency, suggesting that Ca2+ release from intracellular stores is not necessary for NE-induced increase in GABA release. Whereas α1 receptors are coupled to Gq/11 resulting in activation of the phospholipase C (PLC) pathway, NE-mediated facilitation of GABAergic transmission was independent of PLC, protein kinase C, and tyrosine kinase activities. Our results suggest that NE-mediated facilitation of GABAergic function contributes to its antiepileptic effects in the EC.
AB - Whereas the entorhinal cortex (EC) receives noradrenergic innervations from the locus coeruleus of the pons and expresses adrenergic receptors, the function of norepinephrine (NE) in the EC is still elusive. We examined the effects of NE on GABAA receptor-mediated synaptic transmission in the superficial layers of the EC. Application of NE dose-dependently increased the frequency and amplitude of spontaneous inhibitory postsynaptic currents (IPSCs) recorded from the principal neurons in layer II/III through activation of α1 adrenergic receptors. NE increased the frequency and not the amplitude of miniature IPSCs (mIPSCs) recorded in the presence of TTX, suggesting that NE increases presynaptic GABA release with no effects on postsynaptic GABAA receptors. Application of Ca2+ channel blockers (Cd2+ and Ni2+), omission of Ca2+ in the extracellular solution, or replacement of extracellular Na+ with N-methyl-D-glucamine (NMDG) failed to alter NE-induced increase in mIPSC frequency, suggesting that Ca2+ influx through voltage-gated Ca 2+ or other cationic channels is not required. Application of BAPTA-AM, thapsigargin, and ryanodine did not change NE-induced increase in mIPSC frequency, suggesting that Ca2+ release from intracellular stores is not necessary for NE-induced increase in GABA release. Whereas α1 receptors are coupled to Gq/11 resulting in activation of the phospholipase C (PLC) pathway, NE-mediated facilitation of GABAergic transmission was independent of PLC, protein kinase C, and tyrosine kinase activities. Our results suggest that NE-mediated facilitation of GABAergic function contributes to its antiepileptic effects in the EC.
UR - http://www.scopus.com/inward/record.url?scp=36248965176&partnerID=8YFLogxK
U2 - 10.1152/jn.00679.2007
DO - 10.1152/jn.00679.2007
M3 - Article
C2 - 17804573
AN - SCOPUS:36248965176
SN - 0022-3077
VL - 98
SP - 2868
EP - 2877
JO - Journal of neurophysiology
JF - Journal of neurophysiology
IS - 5
ER -