Submitted on February 13, 2007
Accepted on April 7, 2007
Electrophysiological Properties and Subunit Composition of
GABAA Receptors in Patients with Gelastic Seizures and Hypothalamic Hamartoma
Jie Wu1*, Yongchang Chang2, Guohui Li1, Fenqin Xue2, Jamie Dechon1, Kevin Ellsworth1, Qiang Liu1, Kechun Yang1, Nasim Bahadroani3, Chao Zheng1, Jianliang Zhang2, Harold Rekate4, Jong M Rho1, and John F Kerrigan1
1 Neurology, Barrow Neurological Institue, Phoenix, Arizona, United States
2 Neurobiology, Barrow Neurological Institue, Phoenix, Arizona, United States
3 Neurobiology, Barrow Neurological Institute, Phoenix, Arizona, United States
4 Neurosurgery, Barrow Neurological Institute, Phoenix, United States
* To whom correspondence should be addressed. E-mail: Jie.Wu{at}CHW.EDU.
Abnormalities in GABAA receptor structure and/or function have been associated with various forms of epilepsy in both humans and animals. Whether this is true for the patients with gelastic seizures and hypothalamic hamartoma (HH) is unknown. In the present study, we characterized the pharmacological properties and native subunit composition of GABAA receptors on acutely dissociated single neurons from neurosurgical resected HH tissues using patch-clamp, immunocytochemical and RT-PCR techniques. We found that: (1) GABA induced an inward current (IGABA) at a holding potential of -60 mV; (2) IGABA was mimicked by the GABAA receptor agonist muscimol and blocked by the GABAA receptor antagonist bicuculline, suggesting that IGABA was mediated principally through the GABAA receptor; (3) the EC50 and Hill coefficient derived from the IGABA concentration-response curve were 6.8 µM and 1.9, respectively; (4) the current-voltage (I-V) curve was linear at a reversal potential close to zero; and (5) IGABA exhibited low sensitivity to zinc and diazepam, but higher sensitivity to pentobarbital and pregnanolone. Additionally, using Xenopus oocytes microtransplanted with normal human hypothalamic tissue, we confirmed that the functional properties of GABAA receptors were similar to that seen in small isolated HH neurons. Finally, the expression profile of GABAA receptor subunits obtained from normal control human hypothalamic tissue was identical to that from surgically resected human HH tissue. Taken together, our data indicate that GABAA receptors on small HH neurons exhibit normal pharmacosensitivity and subunit composition. These findings bear relevance to a broader understanding of inhibitory neurotransmission in human HH tissue.
