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Paper Information

Journal:   IRANIAN JOURNAL OF PHARMACEUTICAL RESEARCH (IJPR)   May 2004 , Volume 3 , Number Supplement 1; Page(s) 13 To 14.
 
Paper: 

ACTIVATION OF INWARDLY-RECTIFYING K+ CHANNELS IN HYPOTHALAMIC POMC NEURONS: ROLE IN INTEGRATING SYNAPTIC AND METABOLIC INPUT

 
 
Author(s):  IBRAHIM N.*, SMART J.L., RUBINSTEIN M., LOW M.J., KELLY M.J.
 
* 
 
Abstract: 

Hypothalamic proopiomelanocortin (POMC) neurons are critical for controlling homeostatic functions in mammals. We used a transgenic mouse model in which the POMC neurons were labeled with enhanced-green fluorescent protein (EGFP) to perform visualized, whole-cell patch recordings from pre-pubertal female hypothalamic slices. The mouse POMC-EGFP neurons expressed the same endogenous conductance (IA and Ih) that has been described for guinea pig POMC neurons. In addition, the selective opioid receptor agonist DAMGO induced an outward current (maximum of 12.8±1.2 pA), which reversed at EK+, in the majority (85%) of POMC neurons with an EC50 of 102 mM. This response was blocked by the opioid receptor antagonist naloxone with a Ki of 3.1 nM. In addition, the GABAB agonist baclofen (40 mM) caused an outward current (21.6±4.0 pA) that reversed at E K+ in these same neurons. The KATP channel opener diazoxide also induced an outward K+ current (maximum of 18.7±2.2 pA) in the majority (92%) of POMC neurons with an EC50 of 61 mM. The response to diazoxide was blocked by the sulfonylurea tolbutamide, indicating that the POMC neurons express both Kir6.2 and SUR1 channel subunits, which was verified using single cell RT-PCR. This pharmacological and molecular profile suggested that POMC neurons might be sensitive to metabolic inhibition, and indeed, we found that their firing rate varied with changes in glucose concentrations. Therefore, it appears that POMC neurons may function as an integrator of metabolic cues and synaptic input for controlling homeostasis in the mammal.

 
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