Dual regulation of the ATP-sensitive potassium channel by activation of cGMP-dependent protein kinase
| Autor: | Yu-Fung Lin, Yongping Chai |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
endocrine system
Patch-Clamp Techniques Purinones ATP-sensitive potassium channel Physiology Recombinant Fusion Proteins Clinical Biochemistry Carbazoles Biology Nitric Oxide Cell Line chemistry.chemical_compound Adenosine Triphosphate KATP Channels Physiology (medical) Cyclic GMP-Dependent Protein Kinases Animals Humans Nitric Oxide Donors Patch clamp Enzyme Inhibitors Potassium Channels Inwardly Rectifying Protein kinase A Cyclic guanosine monophosphate Neurons Cell biology Biochemistry chemistry cardiovascular system Sulfonylurea receptor Soluble guanylyl cyclase Zaprinast cGMP-dependent protein kinase Nitroso Compounds Signal Transduction |
| Zdroj: | Pflügers Archiv - European Journal of Physiology. 456:897-915 |
| ISSN: | 1432-2013 0031-6768 |
| DOI: | 10.1007/s00424-008-0447-z |
| Popis: | Adenosine triphosphate (ATP)-sensitive potassium (K(ATP)) channels couple cellular metabolic status to membrane electrical activity. In this study, we performed patch-clamp recordings to investigate how cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG) regulates the function of K(ATP) channels, using both transfected human SH-SY5Y neuroblastoma cells and embryonic kidney (HEK) 293 cells. In intact SH-SY5Y cells, the single-channel currents of Kir6.2/sulfonylurea receptor (SUR) 1 channels, a neuronal-type K(ATP) isoform, were enhanced by zaprinast, a cGMP-specific phosphodiesterase inhibitor; this enhancement was abolished by inhibition of PKG, suggesting a stimulatory role of cGMP/PKG signaling in regulating the function of neuronal K(ATP) channels. Similar effects of cGMP accumulation were confirmed in intact HEK293 cells expressing Kir6.2/SUR1 channels. In contrast, direct application of purified PKG suppressed rather than activated Kir6.2/SUR1 channels in excised, inside-out patches, while tetrameric Kir6.2LRKR368/369/370/371AAAA channels expressed without the SUR subunit were not modulated by zaprinast or purified PKG. Lastly, reconstitution of the soluble guanylyl cyclase/cGMP/PKG signaling pathway by generation of nitric oxide led to Kir6.2/SUR1 channel activation in both cell types. Taken together, here, we report novel findings that PKG exerts dual functional regulation of neuronal K(ATP) channels in a SUR subunit-dependent manner, which may provide new means of therapeutic intervention for manipulating neuronal excitability and/or survival. |
| Databáze: | OpenAIRE |
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