scholarly journals Trafficking of BK channel subunits controls arterial contractility

Oncotarget ◽  
2017 ◽  
Vol 8 (63) ◽  
pp. 106149-106150 ◽  
Author(s):  
M. Dennis Leo ◽  
Jonathan H. Jaggar
Keyword(s):  
Bk Channel ◽  
Arterial Contractility

scholarly journals Angiotensin II stimulates internalization and degradation of arterial myocyte plasma membrane BK channels to induce vasoconstriction

2015 ◽  
Vol 309 (6) ◽  
pp. C392-C402 ◽  
Author(s):  
M. Dennis Leo ◽  
Simon Bulley ◽  
John P. Bannister ◽  
Korah P. Kuruvilla ◽  
Damodaran Narayanan ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Angiotensin Ii ◽  
Cerebral Arteries ◽  
Bk Channels ◽  
Bk Channel ◽  
Nitric Oxide Donor ◽  
Ang Ii ◽  
Functional Responses ◽  
Early Endosomes ◽  
Arterial Contractility

Arterial smooth muscle cells (myocytes) express large-conductance Ca2+-activated K+ (BK) channel α and auxiliary β1 subunits that modulate arterial contractility. In arterial myocytes, β1 subunits are stored within highly mobile rab11A-positive recycling endosomes. In contrast, BKα subunits are primarily plasma membrane-localized. Trafficking pathways for BKα and whether physiological stimuli that regulate arterial contractility alter BKα localization in arterial myocytes are unclear. Here, using biotinylation, immunofluorescence resonance energy transfer (immunoFRET) microscopy, and RNAi-mediated knockdown, we demonstrate that rab4A-positive early endosomes traffic BKα to the plasma membrane in myocytes of resistance-size cerebral arteries. Angiotensin II (ANG II), a vasoconstrictor, reduced both surface and total BKα, an effect blocked by bisindolylmaleimide-II, concanavalin A, and dynasore, protein kinase C (PKC), internalization, and endocytosis inhibitors, respectively. In contrast, ANG II did not reduce BKα mRNA, and sodium nitroprusside, a nitric oxide donor, did not alter surface BKα protein over the same time course. MG132 and bafilomycin A, proteasomal and lysosomal inhibitors, respectively, also inhibited the ANG II-induced reduction in surface and total BKα, resulting in intracellular BKα accumulation. ANG II-mediated BK channel degradation reduced BK currents in isolated myocytes and functional responses to iberiotoxin, a BK channel blocker, and NS1619, a BK activator, in pressurized (60 mmHg) cerebral arteries. These data indicate that rab4A-positive early endosomes traffic BKα to the plasma membrane in arterial myocytes. We also show that ANG II stimulates PKC-dependent BKα internalization and degradation. These data describe a unique mechanism by which ANG II inhibits arterial myocyte BK currents, by reducing surface channel number, to induce vasoconstriction.

Modulation of the calcium-activated BK-channel of the inner mitochondrial membrane by hypoxia

2007 ◽  
Vol 34 (S 2) ◽  
Author(s):  
D Siemen ◽  
Y Cheng ◽  
X Gu ◽  
P Bednarczyk ◽  
GG Haddad ◽  
...  
Keyword(s):  
Mitochondrial Membrane ◽  
Bk Channel ◽  
Inner Mitochondrial Membrane

The Yin and Yang of BK Channels in Epilepsy

2018 ◽  
Vol 17 (4) ◽  
pp. 272-279 ◽  
Author(s):  
Yudan Zhu ◽  
Shuzhang Zhang ◽  
Yijun Feng ◽  
Qian Xiao ◽  
Jiwei Cheng ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Bk Channels ◽  
Bk Channel ◽  
Potential Shape ◽  
Yin And Yang ◽  
The Central Nervous System ◽  
Action Potential Shape ◽  
Excitability Of Neurons

Background & Objective: The large conductance calcium-activated potassium (BK) channel, extensively distributed in the central nervous system (CNS), is considered as a vital player in the pathogenesis of epilepsy, with evidence implicating derangement of K+ as well as regulating action potential shape and duration. However, unlike other channels implicated in epilepsy whose function in neurons could clearly be labeled “excitatory” or “inhibitory”, the unique physiological behavior of the BK channel allows it to both augment and decrease the excitability of neurons. Thus, the role of BK in epilepsy is controversial so far, and a growing area of intense investigation. Conclusion: Here, this review aims to highlight recent discoveries on the dichotomous role of BK channels in epilepsy, focusing on relevant BK-dependent pro- as well as antiepileptic pathways, and discuss the potential of BK specific modulators for the treatment of epilepsy.

BK channel openers inhibit migration of human glioma cells

2003 ◽  
Vol 446 (2) ◽  
pp. 248-255 ◽  
Author(s):  
Robert Kraft ◽  
Peter Krause ◽  
Silke Jung ◽  
Daniel Basrai ◽  
Lutz Liebmann ◽  
...  
Keyword(s):  
Glioma Cells ◽  
Bk Channel ◽  
Human Glioma ◽  
Human Glioma Cells

scholarly journals Large-conductance voltage- and Ca2+-activated K+ channel regulation by protein kinase C in guinea pig urinary bladder smooth muscle

2014 ◽  
Vol 306 (5) ◽  
pp. C460-C470 ◽  
Author(s):  
Kiril L. Hristov ◽  
Amy C. Smith ◽  
Shankar P. Parajuli ◽  
John Malysz ◽  
Georgi V. Petkov
Keyword(s):  
Smooth Muscle ◽  
Membrane Potential ◽  
Guinea Pig ◽  
Bk Channels ◽  
Bk Channel ◽  
K Channel ◽  
Channel Activity ◽  
Open Probability ◽  
Channel Regulation ◽  
Pkc Activation

Large-conductance voltage- and Ca2+-activated K+ (BK) channels are critical regulators of detrusor smooth muscle (DSM) excitability and contractility. PKC modulates the contraction of DSM and BK channel activity in non-DSM cells; however, the cellular mechanism regulating the PKC-BK channel interaction in DSM remains unknown. We provide a novel mechanistic insight into BK channel regulation by PKC in DSM. We used patch-clamp electrophysiology, live-cell Ca2+ imaging, and functional studies of DSM contractility to elucidate BK channel regulation by PKC at cellular and tissue levels. Voltage-clamp experiments showed that pharmacological activation of PKC with PMA inhibited the spontaneous transient BK currents in native freshly isolated guinea pig DSM cells. Current-clamp recordings revealed that PMA significantly depolarized DSM membrane potential and inhibited the spontaneous transient hyperpolarizations in DSM cells. The PMA inhibitory effects on DSM membrane potential were completely abolished by the selective BK channel inhibitor paxilline. Activation of PKC with PMA did not affect the amplitude of the voltage-step-induced whole cell steady-state BK current or the single BK channel open probability (recorded in cell-attached mode) upon inhibition of all major Ca2+ sources for BK channel activation with thapsigargin, ryanodine, and nifedipine. PKC activation with PMA elevated intracellular Ca2+ levels in DSM cells and increased spontaneous phasic and nerve-evoked contractions of DSM isolated strips. Our results support the concept that PKC activation leads to a reduction of BK channel activity in DSM via a Ca2+-dependent mechanism, thus increasing DSM contractility.

Reactive oxygen species impair Slo1 BK channel function by altering cysteine-mediated calcium sensing

2004 ◽  
Vol 11 (2) ◽  
pp. 171-178 ◽  
Author(s):  
Xiang Dong Tang ◽  
Maria L Garcia ◽  
Stefan H Heinemann ◽  
Toshinori Hoshi
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Bk Channel ◽  
Oxygen Species ◽  
Channel Function ◽  
Calcium Sensing

scholarly journals A cysteine-rich motif confers hypoxia sensitivity to mammalian large conductance voltage- and Ca-activated K (BK) channel  -subunits

2005 ◽  
Vol 102 (49) ◽  
pp. 17870-17876 ◽  
Author(s):  
C. E. McCartney ◽  
H. McClafferty ◽  
J.-M. Huibant ◽  
E. G. Rowan ◽  
M. J. Shipston ◽  
...  
Keyword(s):  
Bk Channel
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