GLP-1 and Exendin-4 Transiently Enhance GABA(A) Receptor-Mediated Synaptic and Tonic Currents in Rat Hippocampal CA3 Pyramidal Neurons [Elektronisk resurs]
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Korol, Sergiy V. (författare)
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Jin, Zhe (författare)
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Babateen, Omar (författare)
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Birnir, Bryndis (författare)
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Uppsala universitet Medicinska och farmaceutiska vetenskapsområdet (utgivare)
- 2015
- Engelska.
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Ingår i: Diabetes. - 0012-1797. ; 64:1, 79-89
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- GLP-1 is a hormone that stimulates insulin secretion. Receptors for GLP-1 are also found in the brain, including the hippocampus, the centre for memory and learning. Diabetes mellitus is a risk factor for decreased memory functions. We studied effects of GLP-1 and exendin-4, a GLP-1 receptor agonist, on γ-aminobutyric acid (GABA) signaling in hippocampal CA3 pyramidal neurons. GABA is the main inhibitory neurotransmitter and decreases neuronal excitability. GLP-1 (0.01 – 1 nmol/L) transiently enhanced synaptic and tonic currents and the effects were blocked by exendin(9–39). Ten pmol/L GLP-1 increased both the spontaneous inhibitory postsynaptic current (sIPSC) amplitudes and frequency by a factor of 1.8. In 0.1, 1 nmol/L GLP-1 or 10, 50 or 100 nmol/L exendin-4, only the sIPSC frequency increased. The tonic current was enhanced by 0.01 – 1 nmol/L GLP-1 and by 0.5 – 100 nmol/L exendin-4. When action potentials were inhibited by tetrodotoxin (TTX), IPSCs decreased and currents were no longer potentiated by GLP-1 or exendin-4. In contrast, although the tonic current decreased in TTX, it was still enhanced by GLP-1 or exendin-4. The results demonstrate GLP-1 receptor regulation of hippocampal function and are consistent with GLP-1 receptor agonists enhancing GABA A signaling by pre- and postsynaptic mechanisms.
Ämnesord
- Medical and Health Sciences (hsv)
- Health Sciences (hsv)
- Public Health, Global Health, Social Medicine and Epidemiology (hsv)
- Medicin och hälsovetenskap (hsv)
- Hälsovetenskaper (hsv)
- Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi (hsv)
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