Constitutively active and G-protein coupled inward rectifier K+ channels: Kir2.0 and Kir3.0

Stanfield, Peter; Nakajima, Shigehiro; Nakajima, Yoshiaki

doi:10.1007/bfb0116431

Cited by 142 publications

(158 citation statements)

References 531 publications

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“…PCR analysis of human islets revealed expression of KCNJ12 (Kir2.2; 90% of the transcripts) and KCNJ4 (Kir2.3; 10% of the transcripts) and it is tempting to attribute the observed inwardly rectifying K + current to these channels. In cardiomyocytes, inwardly rectifying K + channels stabilise the resting membrane potential and maintain the plateau phase of the prolonged action potentials [29,30]. The finding that blockade of the inwardly rectifying K + current by Ba 2+ resulted in the emergence of chaotic membrane potential oscillations suggests a role for inward rectifiers in membrane potential stabilisation in delta cells.…”

Section: Discussionmentioning

confidence: 99%

Somatostatin release, electrical activity, membrane currents and exocytosis in human pancreatic delta cells

et al. 2009

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Aims/hypothesis The aim of this study was to characterise electrical activity, ion channels, exocytosis and somatostatin release in human delta cells/pancreatic islets. Methods Glucose-stimulated somatostatin release was measured from intact human islets. Membrane potential, currents and changes in membrane capacitance (reflecting exocytosis) were recorded from individual human delta cells identified by immunocytochemistry. Results Somatostatin secretion from human islets was stimulated by glucose and tolbutamide and inhibited by diazoxide. Human delta cells generated bursting or sporadic electrical activity, which was enhanced by tolbutamide but unaffected by glucose. Delta cells contained a tolbutamide-insensitive, Ba 2+ -sensitive inwardly rectifying K + current and two types of voltagegated K + currents, sensitive to tetraethylammonium/ stromatoxin (delayed rectifying, Kv2.1/2.2) and 4-aminopyridine (A current). Voltage-gated tetrodotoxin (TTX)-sensitive Na + currents contributed to the action potential upstroke but TTX had no effect on somatostatin release. Delta cells are equipped with Ca 2+ channels blocked by isradipine (L), ω-agatoxin (P/Q) and NNC 55-0396 (T). Blockade of any of these channels interferes with delta cell electrical activity and abolishes glucose-stimulated somatostatin release. Capacitance measurements revealed a slow component of depolarisation-evoked exocytosis sensitive to ω-agatoxin. Conclusions/interpretation Action potential firing in delta cells is modulated by ATP-sensitive K + -channel activity. The membrane potential is stabilised by Ba 2+ -sensitive inwardly rectifying K + channels. Voltage-gated L-and T-type Ca 2+ channels are required for electrical activity, whereas Na + currents and P/Q-type Ca 2+ channels contribute to (but are not necessary for) the upstroke of the action potential. Action potential repolarisation is mediated by A-type and Kv2.1/2.2 K + channels. Exocytosis is tightly linked to Ca 2+ -influx via P/Q-type Ca 2+ channels. Glucose stimulation of somatostatin secretion involves both K ATP channel-dependent and -independent processes.

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Section: Discussionmentioning

confidence: 99%

Somatostatin release, electrical activity, membrane currents and exocytosis in human pancreatic delta cells

et al. 2009

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“…9,10 Kir channels are the ion channel family, whose dependence on phosphoinositides, and in particular on phosphatidylinositol bisphosphate (PIP 2 ) that is the most abundant plasma membrane phosphoinositide, has been studied most comprehensively (reviewed in refs. [11][12][13][14][15][16][17][18][19]. Despite intense studies of Kir channel interactions with phosphoinositides, the number of PIP 2 molecules controlling channel activity is not known.…”

Section: Introductionmentioning

confidence: 99%

Stoichiometry of Kir channels with phosphatidylinositol bisphosphate

Jin

Sui²,

Rosenhouse‐Dantsker³

et al. 2008

Channels

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Phosphatidylinositol bisphosphate (PIP 2 ) is the most abundant phosphoinositide in the plasma membrane of cells and its interaction with many ion channel proteins has proven to be a critical factor enabling ion channel gating. All members of the inwardly rectifying potassium (Kir) channel family depend on PIP 2 for their activity, displaying distinct affinities and stereospecificities of interaction with the phosphoinositide. Here, we explored the stoichiometry of Kir channels with PIP 2 . We first showed that PIP 2 regulated the activity of Kir3.4 channels mainly by altering their bursting behavior. Detailed burst analysis indicates that the channels assumed up to four open states and a connectivity of four between open and closed states depending on the available PIP 2 levels. Moreover, by controlling the number of PIP 2 -sensitive subunits in the stoichiometry of a tetrameric Kir2.1 channel, we showed that characteristic channel activity was obtained when at least two wild-type subunits were present. Our studies support a kinetic model for gating of Kir channels by PIP 2 , where each of the four open states corresponds to the channel activated by one to four PIP 2 molecules.

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“…Kir3.1 channels are unable to traffic to the cell surface in the absence of other Kir3 channels and must assemble with Kir3.2, Kir3.3 or Kir3.4 to form functional heteromeric channels. 18 Kir3.2, on the other hand, can form functional homotetramers. Because Kir3.1 lacks a PDZ binding motif, we predicted that Kir3.1 expressed alone in HEK293 cells would not be affected by coexpressed SNX27.…”

Section: Introductionmentioning

confidence: 99%