scholarly journals A novel ion conducting route besides the central pore in an inherited mutant of G‐protein‐gated inwardly rectifying K + channel

2021 ◽  
Author(s):  
I‐Shan Chen ◽  
Jodene Eldstrom ◽  
David Fedida ◽  
Yoshihiro Kubo
Keyword(s):  
G Protein ◽  
K Channel ◽  
Central Pore ◽  
Ion Conducting ◽  
Inwardly Rectifying

scholarly journals A novel ion conducting route besides the central pore in an inherited mutant of G-protein-gated inwardly rectifying K+ channel

2021 ◽  
Author(s):  
I-Shan Chen ◽  
Jodene Eldstrom ◽  
David Fedida ◽  
Yoshihiro Kubo
Keyword(s):  
G Protein ◽  
Structural Changes ◽  
Single Channel ◽  
Ion Selectivity ◽  
K Channel ◽  
Girk Channels ◽  
Electrode Voltage ◽  
Ion Conducting ◽  
Inwardly Rectifying ◽  
Better Than

G-protein-gated inwardly rectifying K+ (GIRK; Kir3.x) channels play important physiological roles in various organs. Some of the disease-associated mutations of GIRK channels are known to induce loss of K+ selectivity but their structural changes remain unclear. In this study, we investigated the mechanisms underlying the abnormal ion selectivity of inherited GIRK mutants. By the two-electrode voltage-clamp analysis of GIRK mutants heterologously expressed in Xenopus oocytes, we observed that Kir3.2 G156S permeates Li+ better than Rb+, while T154del or L173R of Kir3.2 and T158A of Kir3.4 permeate Rb+ better than Li+, suggesting a unique conformational change in the G156S mutant. Applications of blockers of the selectivity filter (SF) pathway, Ba2+ or Tertiapin-Q (TPN-Q), remarkably increased the Li+-selectivity of Kir3.2 G156S but did not alter those of the other mutants. In single-channel recordings of Kir3.2 G156S expressed in mouse fibroblasts, two types of events were observed, one attributable to a TPN-Q sensitive K+ current and the second a TPN-Q resistant Li+ current. The results show that a novel Li+ permeable and blocker-resistant pathway exists in G156S in addition to the SF pathway. Mutations in the pore helix (PH), S148F and T151A, also induced high Li+ permeation. Our results demonstrate that the mechanism underlying the loss of K+ selectivity of Kir3.2 G156S involves formation of a novel ion permeation pathway besides the SF pathway, which allows permeation of various species of cations.

scholarly journals Familial Sinus Node Disease Caused by a Gain of GIRK (G-Protein Activated Inwardly Rectifying K + Channel) Channel Function

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Johanna Kuß ◽  
Birgit Stallmeyer ◽  
Matthias Goldstein ◽  
Susanne Rinné ◽  
Christiane Pees ◽  
...  
Keyword(s):  
G Protein ◽  
Sinus Node ◽  
K Channel ◽  
Channel Function ◽  
Node Disease ◽  
Sinus Node Disease ◽  
Inwardly Rectifying

scholarly journals Intrinsic gating properties of a cloned G protein-activated inward rectifier K+ channel.

1995 ◽  
Vol 106 (1) ◽  
pp. 1-23 ◽  
Author(s):  
C A Doupnik ◽  
N F Lim ◽  
P Kofuji ◽  
N Davidson ◽  
H A Lester
Keyword(s):  
G Protein ◽  
K Channel ◽  
Extrinsic Factors ◽  
Time Resolved ◽  
Time Constants ◽  
Protein Activation ◽  
G Protein Activation ◽  
Voltage Dependent ◽  
Current Activation ◽  
Inwardly Rectifying

The voltage-, time-, and K(+)-dependent properties of a G protein-activated inwardly rectifying K+ channel (GIRK1/KGA/Kir3.1) cloned from rat atrium were studied in Xenopus oocytes under two-electrode voltage clamp. During maintained G protein activation and in the presence of high external K+ (VK = 0 mV), voltage jumps from VK to negative membrane potentials activated inward GIRK1 K+ currents with three distinct time-resolved current components. GIRK1 current activation consisted of an instantaneous component that was followed by two components with time constants tau f approximately 50 ms and tau s approximately 400 ms. These activation time constants were weakly voltage dependent, increasing approximately twofold with maximal hyperpolarization from VK. Voltage-dependent GIRK1 availability, revealed by tail currents at -80 mV after long prepulses, was greatest at potentials negative to VK and declined to a plateau of approximately half the maximal level at positive voltages. Voltage-dependent GIRK1 availability shifted with VK and was half maximal at VK -20 mV; the equivalent gating charge was approximately 1.6 e-. The voltage-dependent gating parameters of GIRK1 did not significantly differ for G protein activation by three heterologously expressed signaling pathways: m2 muscarinic receptors, serotonin 1A receptors, or G protein beta 1 gamma 2 subunits. Voltage dependence was also unaffected by agonist concentration. These results indicate that the voltage-dependent gating properties of GIRK1 are not due to extrinsic factors such as agonist-receptor interactions and G protein-channel coupling, but instead are analogous to the intrinsic gating behaviors of other inwardly rectifying K+ channels.

scholarly journals Pancreatic Islet Cells Express a Family of Inwardly Rectifying K+Channel Subunits Which Interact to Form G-protein-activated Channels

1995 ◽  
Vol 270 (44) ◽  
pp. 26086-26091 ◽  
Author(s):  
Jorge Ferrer ◽  
Colin G. Nichols ◽  
Elena N. Makhina ◽  
Lawrence Salkoff ◽  
Josh Bernstein ◽  
...  
Keyword(s):  
G Protein ◽  
Pancreatic Islet ◽  
Islet Cells ◽  
K Channel ◽  
Pancreatic Islet Cells ◽  
Inwardly Rectifying
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