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Modulation of the serotonin-activated K+ channel by G protein subunits and nucleotides in rat hippocampal neurons

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In hippocampal neurons, 5-hydroxytryptamine (5-HT) activates an inwardly rectifying K+ current via G protein. We identified the K+ channel activated by 5-HT (K5-HT channel) and studied the effects of G protein subunits and nucleotides on the K+ channel kinetics in adult rat hippocampal neurons. In inside-out patches with 10 μm 5-HT in the pipette, application of GTP (100 μm) to the cytoplasmic side of the membrane activated an inwardly rectifying K+ channel with a slope conductance of 36±1 pS (symmetrical 140 mm K+) at −60 mV and a mean open time of 1.1±0.1 msec (n=5). Transducin βγ activated the (K5-HT) channels and this was reversed by α-GDP. Whether the K5-HT channel was activated endogenously (GTP, GTPγS) or exogenously (βγ), the presence of 1 mm ATP resulted in a ∼4-fold increase in channel activity due in large part to the prolongation of the open time duration. These effects of ATP were irreversible and not mimicked by AMPPMP, suggesting that phosphorylation might be involved. However, inhibitors of protein kinases A and C (H-7, staurosporine) and tyrosine kinase (tyrphostin 25) failed to block the effect of ATP. These results show that Gβγ activates the G protein-gated K+ channel in hippocampal neurons, and that ATP modifies the gating kinetics of the channel, resulting in increased open probability via as yet unknown pathways.

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Oh, U., Ho, Y.-. & Kim, D. Modulation of the serotonin-activated K+ channel by G protein subunits and nucleotides in rat hippocampal neurons. J. Membarin Biol. 147, 241–253 (1995). https://doi.org/10.1007/BF00234522

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Key words

  • Serotonin
  • G-protein
  • Hippocampus
  • βγ subunit
  • ATP