Synergistic interplay of Gβγ and phosphatidylinositol 4,5-bisphosphate dictates Kv7.4 channel activity
| Autor: | Iain A. Greenwood, Vincenzo Barrese, Jennifer B. Stott, Oleksandr V. Povstyan |
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| Přispěvatelé: | Povstyan, O. V., Barrese, V., Stott, J. B., Greenwood, I. A. |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Phosphatidylinositol 4 5-Diphosphate KCNQ Potassium Channel G protein Physiology Clinical Biochemistry Stimulation Biology Phosphatidylinositols Cell Line 03 medical and health sciences chemistry.chemical_compound KCNQ 0302 clinical medicine HEK293 Cell PIP2 GTP-Binding Proteins Physiology (medical) Ion channel regulation Humans Phosphatidylinositol Potassium channel Receptor G-protein βγ Mechanosensation KCNQ Potassium Channels HEK 293 cells PIP Cell biology 030104 developmental biology HEK293 Cells Biochemistry Phosphatidylinositol 4 5-bisphosphate chemistry lipids (amino acids peptides and proteins) Ion Channel Gating 030217 neurology & neurosurgery Ion Channels Receptors and Transporters GTP-Binding Protein Human |
| Zdroj: | Pflugers Archiv |
| ISSN: | 1432-2013 0031-6768 |
| Popis: | Kv7.4 channels are key determinants of arterial contractility and cochlear mechanosensation that, like all Kv7 channels, have an obligatory requirement for phosphatidylinositol 4,5-bisphosphate (PIP2). βγ G proteins (Gβγ) have been identified as novel positive regulators of Kv7.4. The present study ascertained whether Gβγ increased Kv7.4 open probability through an increased sensitivity to PIP2. In HEK cells stably expressing Kv7.4, PIP2 or Gβγ increased open probability in a concentration dependent manner. Depleting PIP2 prevented any Gβγ-mediated stimulation whilst an array of Gβγ inhibitors prohibited any PIP2-induced current enhancement. A combination of PIP2 and Gβγ at sub-efficacious concentrations increased channel open probability considerably. The stimulatory effects of three Kv7.2-7.5 channel activators were also lost by PIP2 depletion or Gβγ inhibitors. This study alters substantially our understanding of the fundamental processes that dictate Kv7.4 activity, revealing a more complex and subtle paradigm where the reliance on local phosphoinositide is dictated by interaction with Gβγ. |
| Databáze: | OpenAIRE |
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