scholarly journals Gβγ-activated Inwardly Rectifying K+(GIRK) Channel Activation Kinetics via Gαiand Gαo-coupled Receptors Are Determined by Gα-specific Interdomain Interactions That Affect GDP Release Rates

2004 ◽  
Vol 279 (28) ◽  
pp. 29787-29796 ◽  
Author(s):  
Qingli Zhang ◽  
Alec Dickson ◽  
Craig A. Doupnik
Keyword(s):  
Release Rates ◽  
Channel Activation ◽  
Activation Kinetics ◽  
Girk Channel ◽  
Interdomain Interactions ◽  
Inwardly Rectifying

Interplay Between Activation of GIRK Current and Deactivation ofI h Modifies Temporal Integration of Excitatory Input in CA1 Pyramidal Cells

2003 ◽  
Vol 89 (4) ◽  
pp. 2238-2244 ◽  
Author(s):  
Tomoko Takigawa ◽  
Christian Alzheimer
Keyword(s):  
Temporal Integration ◽  
Pyramidal Cells ◽  
Progressive Increase ◽  
Excitatory Input ◽  
Channel Activation ◽  
Ca1 Pyramidal Cells ◽  
Girk Channel ◽  
Inwardly Rectifying ◽  
Apical Dendrites ◽  
Kinetics Of

Trains of brief iontophoretic glutamate pulses were delivered onto the apical dendrites of CA1 pyramidal cells at variable frequencies (3–100 Hz) to examine how the activation of a G protein–activated, inwardly rectifying K+ (GIRK) conductance alters the postsynaptic processing of repetitive excitatory input. Application of the GIRK channel agonist baclofen (20 μM) reduced the amplitude of individual glutamate-evoked postsynaptic potentials (GPSPs) and attenuated summation of GPSPs so that higher stimulus intensities were required to fire the cell. Notably, GIRK channel activation not only decreased GPSPs, but also suppressed the subsequent afterhyperpolarization (AHP), which arises from a transient deactivation of the hyperpolarization-activated cation current ( I h). Voltage-clamp recordings ruled out a direct modulatory action of baclofen on I h. GIRK channel activation alone accounts for AHP suppression, firstly because, with smaller GPSP amplitudes, fewer I h channels are deactivated, resulting in a diminished AHP, and secondly because, owing to its progressive increase in the hyperpolarizing direction, the GIRK conductance shunts a large portion of the remaining AHP. We provide experimental evidence that the suppression of the I h-dependent AHP by GIRK channel activation bears particular significance on the processing of repetitive excitatory inputs at frequencies at which the deactivation kinetics of I h exert a prominent depressing effect. In functional terms, activation of GIRK current not only produces a time-independent mitigation of incoming excitatory input, which results directly from the opening of an instantaneous K+ conductance, but might also cause a time-dependent redistribution of synaptic weight within a stimulus train, which we link to an interplay with the deactivation of I h.

Rapid desensitization of G protein-gated inwardly rectifying K+ currents is determined by G protein cycle

2004 ◽  
Vol 287 (1) ◽  
pp. C182-C191 ◽  
Author(s):  
Joanne L. Leaney ◽  
Amy Benians ◽  
Sean Brown ◽  
Muriel Nobles ◽  
David Kelly ◽  
...  
Keyword(s):  
G Protein ◽  
Competitive Inhibition ◽  
Similar Degree ◽  
Channel Activation ◽  
Girk Channels ◽  
Membrane Hyperpolarization ◽  
Hek 293 ◽  
Fast Activation ◽  
Inwardly Rectifying ◽  
Stimulation Of

Activation of G protein-gated inwardly rectifying K+ (GIRK) channels, found in the brain, heart, and endocrine tissue, leads to membrane hyperpolarization that generates neuronal inhibitory postsynaptic potentials, slows the heart rate, and inhibits hormone release. During stimulation of Gi/o-coupled receptors and subsequent channel activation, it has been observed that the current desensitizes. In this study we examined mechanisms underlying fast desensitization of cloned heteromeric neuronal Kir3.1+3.2A and atrial Kir3.1+3.4 channels and also homomeric Kir3.0 currents in response to stimulation of several Gi/o G protein-coupled receptors (GPCRs) expressed in HEK-293 cells (adenosine A1, adrenergic α2A, dopamine D2S, M4 muscarinic, and GABAB1b/2 receptors). We found that all agonist-induced currents displayed a similar degree of desensitization except the adenosine A1 receptor, which exhibits an additional desensitizing component. Using the nonhydrolyzable GTP analog guanosine 5′- O-(3-thiotriphosphate) (GTPγS), we found that this is due to a receptor-dependent, G protein-independent process. Using Ca2+ imaging we showed that desensitization is unlikely to be accounted for solely by phospholipase C activation and phosphatidylinositol 4,5-bisphosphate (PIP2) hydrolysis. We examined the contribution of the G protein cycle and found the following. First, agonist concentration is strongly correlated with degree of desensitization. Second, competitive inhibition of GDP/GTP exchange by using nonhydrolyzable guanosine 5′- O-(2-thiodiphosphate) (GDPβS) has two effects, a slowing of channel activation and an attenuation of the fast desensitization phenomenon. Finally, using specific Gα subunits we showed that ternary complexes with fast activation rates display more prominent desensitization than those with slower activation kinetics. Together our data suggest that fast desensitization of GIRK currents is accounted for by the fundamental properties of the G protein cycle.

scholarly journals Bidirectional influence of limbic GIRK channel activation on innate avoidance behavior

2021 ◽  
pp. JN-RM-2787-20
Author(s):  
Baovi N. Vo ◽  
Ezequiel Marron Fernandez de Velasco ◽  
Timothy R. Rose ◽  
Hannah Oberle ◽  
Haichang Luo ◽  
...  
Keyword(s):  
Avoidance Behavior ◽  
Channel Activation ◽  
Girk Channel

scholarly journals Block of inward rectification by intracellular H+ in immature oocytes of the starfish Mediaster aequalis.

1982 ◽  
Vol 79 (1) ◽  
pp. 115-130 ◽  
Author(s):  
W J Moody ◽  
S Hagiwara
Keyword(s):  
Intracellular Ph ◽  
Voltage Dependence ◽  
Sea Water ◽  
Inward Rectification ◽  
Activation Kinetics ◽  
Internal Ph ◽  
A Site ◽  
The Relationship ◽  
Inwardly Rectifying ◽  
Kinetics Of

Intracellular pH was recorded in immature starfish oocytes using pH-sensitive microelectrodes, and inwardly rectifying potassium currents were measured under voltage clamp. When the intracellular pH was lowered using acetate-buffered artificial sea water from the normal value of 7.09 to 5.9, inward rectification was completely blocked. The relationship between inward rectification and internal pH between 7.09 and 5.9 could be fit by a titration curve for the binding of three H ions to a site with a pK of 6.26 to block the channel. The H+ block showed no voltage dependence, and the activation kinetics of the inwardly rectifying currents were not affected by the changes in internal pH.

Repeat I of the dihydropyridine receptor is critical in determining calcium channel activation kinetics

Nature ◽  
1991 ◽  
Vol 352 (6338) ◽  
pp. 800-803 ◽  
Author(s):  
Tsutomu Tanabe ◽  
Brett A. Adams ◽  
Shosaku Numa ◽  
Kurt G. Beam
Keyword(s):  
Calcium Channel ◽  
Dihydropyridine Receptor ◽  
Channel Activation ◽  
Activation Kinetics

Human Adrenal Glomerulosa Cells Express K2P and GIRK Potassium Channels that are inhibited by AngII and ACTH

2021 ◽  
Author(s):  
John J. Enyeart ◽  
Judith A. Enyeart
Keyword(s):  
G Protein ◽  
Zona Glomerulosa ◽  
Time Dependent ◽  
Aldosterone Secretion ◽  
Girk Channels ◽  
Whole Cell ◽  
Whole Cell Patch Clamp ◽  
Girk Channel ◽  
Inwardly Rectifying ◽  
G Protein Coupled

In whole-cell patch clamp recordings, it was discovered that normal human adrenal zona glomerulosa (AZG) cells express members of the three major families of K+ channels. Among these are a two pore (K2P) leak-type and a G-protein-coupled, inwardly-rectifying (GIRK) channel, both inhibited by peptide hormones that stimulate aldosterone secretion. The K2P current displayed properties identifying it as TREK-1 (KCNK2). This outwardly-rectifying current was activated by arachidonic acid and inhibited by angiotensin II (AngII), adrenocorticotrophic hormone (ACTH), and forskolin. The activation and inhibition of TREK-1 was coupled to AZG cell hyperpolarization and depolarization, respectively. A second K2P channel, TASK-1 (KCNK3), was expressed at a lower density in AZG cells. Human AZG cells also express inwardly rectifying K+ current(s) (KIR) that include quasi-instantaneous and time-dependent components. This is the first report demonstrating the presence of KIR in whole cell recordings from AZG cells of any species. The time-dependent current was selectively inhibited by AngII, and ACTH, identifying it as a G protein-coupled (GIRK) channel, most likely KIR3.4 (KCNJ5). The quasi-instantaneous KIR current was not inhibited by AngII or ACTH, and may be a separate non-GIRK current. Finally, AZG cells express a voltage-gated, rapidly inactivating K+ current whose properties identified as KV1.4 (KCNA4), a conclusion confirmed by Northern blot. These findings demonstrate that human AZG cells express K2P and GIRK channels whose inhibition by AngII and ACTH are likely coupled to depolarization-dependent secretion. They further demonstrate that human AZG K+ channels differ fundamentally from the widely adopted rodent models for human aldosterone secretion.

scholarly journals Evidence for a Discrete Alcohol Pocket Mediating GIRK Channel Activation

2009 ◽  
Vol 96 (3) ◽  
pp. 463a
Author(s):  
Prafulla Aryal ◽  
Hay Dvir ◽  
Senyon Choe ◽  
Paul A. Slesinger
Keyword(s):  
Channel Activation ◽  
Girk Channel

scholarly journals G-protein–gated inwardly rectifying potassium channels regulate ADP-induced cPLA2 activity in platelets through Src family kinases

Blood ◽  
2006 ◽  
Vol 108 (9) ◽  
pp. 3027-3034 ◽  
Author(s):  
Haripriya Shankar ◽  
Bryan N. Kahner ◽  
Janani Prabhakar ◽  
Parth Lakhani ◽  
Soochong Kim ◽  
...  
Keyword(s):  
Potassium Channels ◽  
G Protein ◽  
P2y Receptors ◽  
Null Mouse ◽  
Channel Blockers ◽  
Functional Responses ◽  
Kinase Activation ◽  
Girk Channel ◽  
Inwardly Rectifying Potassium Channels ◽  
Inwardly Rectifying

Abstract ADP-induced TXA2 generation requires the costimulation of P2Y1, P2Y12, and the GPIIb/IIIa receptors. Signaling events downstream of the P2Y receptors that contribute to ADP-induced TXA2 generation have not been clearly delineated. In this study, we have investigated the role of G-protein–gated inwardly rectifying potassium channels (GIRKs), a recently identified functional effector for the P2Y12 receptor, in the regulation of ADP-induced TXA2 generation. At 10-μM concentrations, the 2 structurally distinct GIRK channel blockers, SCH23390 and U50488H, caused complete inhibition of ADP-induced cPLA2 phosphorylation and TXA2 generation, without affecting the conversion of AA to TXA2 or ADP-induced primary platelet aggregation in aspirin-treated platelets. In addition, Src family kinase selective inhibitors abolished 2MeSADP-mediated cPLA2 phosphorylation and TXA2 generation. Furthermore, these GIRK channel blockers completely blocked Gi-mediated Src kinase activation, suggesting that GIRK channels are upstream of Src family tyrosine kinase activation. In weaver mouse platelets, which have dysfunctional GIRK2 subunits, ADP-induced TXA2 generation was impaired. However, we did not observe any defect in 2MeSADP-induced platelet functional responses in GIRK2-null mouse platelets, suggesting that functional channels composed of other GIRK subunits contribute to ADP-induced TXA2 generation, via the regulation of the Src and cPLA2 activity.

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