Journal
ELIFE
Volume 3, Issue -, Pages -Publisher
ELIFE SCIENCES PUBLICATIONS LTD
DOI: 10.7554/eLife.03671
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Funding
- Howard Hughes Medical Institute
- National Institute of General Medical Sciences [NIHGM43949]
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GIRK channels control spike frequency in atrial pacemaker cells and inhibitory potentials in neurons. By directly responding to G proteins, PIP2 and Na+, GIRK is under the control of multiple signaling pathways. In this study, the mammalian GIRK2 channel has been purified and reconstituted in planar lipid membranes and effects of G alpha, G beta gamma, PIP2 and Na+ analyzed. G beta gamma and PIP2 must be present simultaneously to activate GIRK2. Na+ is not essential but modulates the effect of G beta gamma and PIP2 over physiological concentrations. G alpha(i1)(GTP gamma S) has no effect, whereas G alpha(i1)(GDP) closes the channel through removal of G beta gamma. In the presence of G beta gamma, GIRK2 opens as a function of PIP2 mole fraction with Hill coefficient 2.5 and an affinity that poises GIRK2 to respond to natural variations of PIP2 concentration. The dual requirement for G beta gamma and PIP2 can help to explain why GIRK2 is activated by G(i/o), but not G(q) coupled GPCRs.
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