Zinc modulation of glycine receptors in acutely isolated rat CA3 neurons.
Glycine and GABA are the primary inhibitory neurotransmitters in the spinal cord and brain stem, with glycine exerting its physiological roles by activating strychnine-sensitive ionotropic receptors. Glycine receptors are also expressed in the brain, including the cortex and hippocampus, but their physiological roles and pharmacological properties are largely unknown. Here, we report the pharmacological properties of functional glycine receptors in acutely isolated rat CA3 neurons using conventional whole-cell patch clamp techniques. Both glycine and taurine, which are endogenous agonists of glycine receptors, elicited Cl(-) currents in a concentration-dependent manner. The glycine-induced current (I(Gly)) was inhibited by strychnine, picrotoxin or cyclothiazide in a concentration-dependent manner. At lower concentrations (0.01-1 microM), ICS-205,930 potentiated I(Gly), but at higher concentrations (>10 microM) it inhibited I(Gly). These pharmacological properties strongly suggest that CA3 neurons express functional strychnine-sensitive glycine receptors containing alpha2 subunits. Furthermore, at lower concentrations (1-30 microM), Zn(2+) potentiated I(Gly), but at higher concentrations (>100 microM) it inhibited I(Gly). Considering that Zn(2+) is synaptically co-released with glutamate from mossy fiber terminals that make excitatory synapses onto CA3 neurons, these results suggest that endogenous Zn(2+) modulation of these glycine receptors may have an important role in the excitability of CA3 neurons.
Park
Eun-Joo
EJ
Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu, Republic of Korea.
Choi
In-Sun
IS
Cho
Jin-Hwa
JH
Nakamura
Michiko
M
Lee
Jong-Ju
JJ
Lee
Maan-Gee
MG
Choi
Byung-Ju
BJ
Moorhouse
Andrew J
AJ
Jang
Il-Sung
IS
D000818:Animals; D001581:Benzothiadiazines / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018009:Receptors, Glycine / Q000187:drug effects*; D013331:Strychnine / Q000494:pharmacology; D000077526:Tropisetron; D015032:Zinc / Q000494:pharmacology*
D001581:Benzothiadiazines; D007211:Indoles; D018009:Receptors, Glycine; D000077526:Tropisetron; D013331:Strychnine; D015032:Zinc; C004639:cyclothiazide