New insights into the mechanisms underlying AF have identified promising new approaches, including the modulation of atrium-specific ion channels, connexins and the ryanodine receptor, the prevention of remodelling processes that lead to the arrhythmia as well as specific molecular events involved in arrhythmia generation. (nature.com)
Proteins5
The ability of ion channels to accomplish these three physiological functions also requires the housekeeping operation of another class of membrane proteins, the transporters and pumps, to set up standing ion concentration gradients across cell membranes. (scholarpedia.org)
Ion channels have many features of typical membrane proteins. (scholarpedia.org)
Like other signaling proteins, ion channels are flexible molecules that undergo conformational changes between open (active) and closed (inactive) states. (scholarpedia.org)
The beta cell KATP channel is a complex of two proteins: Kir6.2 and SUR1. (ox.ac.uk)
Functional1
In a previous study we identified an extensive gating network within the inwardly rectifying Kir1.1 (ROMK) channel by combining systematic scanning mutagenesis and functional analysis with structural models of the channel in the closed, pre-open and open states. (philipwfowler.me)
The majority of channels have three, four, or five homologous or identical subunits, arranged in circular symmetry, forming a single aqueous pore at the axial intersection ( Figure 2 ). (scholarpedia.org)
However, one set of channels (ClC chloride channels) has two homologous subunits forming one pore in each of the subunits. (scholarpedia.org)
Perhaps there are 500 genes for pore-forming and accessory subunits of channels. (scholarpedia.org)
In addition many of these channels have smaller accessory subunits that typically do not contribute to the actual pore. (scholarpedia.org)
Plays a key role2
This asymmetry in potassium ion conductance plays a key role in the excitability of muscle cells and neurons. (wikipedia.org)
The ATP-sensitive K+-channel (KATP channel) plays a key role in insulin secretion from pancreatic beta cells. (ox.ac.uk)
Gene2
Potassium inwardly-rectifying channel, subfamily J, member 4, also known as KCNJ4 or Kir2.3, is a human gene. (wikipedia.org)
The protein encoded by this gene is an integral membrane protein and member of the inward rectifier potassium channel family. (wikipedia.org)
Pore2
The former is an ATP-sensitive K+-selective pore, whereas SUR1 is a channel regulator that endows Kir6.2 with sensitivity to sulfonylureas. (ox.ac.uk)
Our results suggest that this may be because Kir6.2, which is expressed in the heart, forms the pore of the cardiac KATP channel. (ox.ac.uk)
Cardiac1
KATP channels also are found in the heart where they are involved in the response to cardiac ischemia: they also are blocked by phentolamine. (ox.ac.uk)
Signals4
His studies demonstrated that chronic psychological stress profoundly disrupts inward-rectifier potassium channel-mediated neurovascular coupling, and revealed that the brain's capillary network constitutes a vast 'sensory web', capable of translating local neural activity into vasodilatory electrical signals. (umaryland.edu)
These signals are then rapidly transmitted along capillaries to relax larger upstream arterioles and direct blood flow to active neurons. (umaryland.edu)
The headstage also provides an integrated stimulator, which can generate current or voltage stimulation signals on three independent channels (two for MEA2100-256-Systems) per MEA slot. (multichannelsystems.com)
Tom's graduate studies were sponsored by a Biotechnology and Biological Sciences Research Council (BBSRC) Collaborative Award in Science and Engineering (CASE) fellowship, with Boehringer Ingelheim as an industrial sponsor, and focused on the role of the astrocytic intermediate-conductance calcium-activated potassium channel in neurovascular coupling. (umaryland.edu)
Here, his work (sponsored by two American Heart Association Founder's Affiliate Postdoctoral Fellowships) focused on the role of vascular ion channels and G-protein coupled receptors in the control of brain blood flow. (umaryland.edu)
Figure 1: General mechanisms of AF and role of ion channels for AF stabilization. (nature.com)
20171
Longden T , Dabertrand F, Koide M, Gonzales A, Tykocki N, Brayden J, Hill-Eubanks D, Nelson M (2017) " Capillary K+-sensing initiates retrograde hyperpolarization to locally increase cerebral blood flow " Nature Neuroscience , 20: 717-726. (umaryland.edu)
Sensors2
Longden T , Nelson M (2015) " Vascular Inward Rectifier K+ Channels as External K+ Sensors in the Control of Cerebral Blood Flow " Microcirculation , 22(3): 183-196. (umaryland.edu)
The sensors couple to the channel gates to control the probability that they open or close. (scholarpedia.org)
Function1
Longden T , Dabertrand F, Hill-Eubanks D, Hammack S, Nelson M (2014) " Stress-Induced Glucocorticoid Signaling Remodels Neurovascular Coupling Through Impairment of Cerebrovascular Inwardly Rectifying K+ Channel Function " Proceedings of the National Academy of Sciences USA , 111(20): 7462-7. (umaryland.edu)
Protein1
The encoded protein has a small unitary conductance compared to other members of this protein family. (wikipedia.org)
Small1
They open and close in response to stimuli, gating the flow of specific small ions. (scholarpedia.org)
Closely1
These results suggest that the structure of the transition state (TS), which connects the pre-open and closed states of the channel, more closely resembles the structure of the pre-open state. (philipwfowler.me)
Targets1
Figure 7: Ion channel bioprocessing and trafficking as potential targets for drug development. (nature.com)
Activity1
Instead, our results argue that phentolamine may interact directly with Kir6.2 to produce a voltage-independent reduction in channel activity. (ox.ac.uk)
Muscle1
Since the flow of ions moves charge and constitutes an electric current, channel opening and closing underlie all electrical signaling of electrically excitable cells such as nerve and muscle. (scholarpedia.org)
Ion concentration gradients and electrical forces drive the flow of ions through channel pores. (scholarpedia.org)
Control1
Longden T , Hill-Eubanks D, Nelson M (2016) " Ion Channel Networks in the Control of Cerebral Blood Flow " Journal of Cerebral Blood Flow & Metabolism , 36(3): 492-512. (umaryland.edu)
Structure1
Figure 4: K + channel structure-based blocking drugs. (nature.com)
Open1
This extensive network appeared to stabilize the open and pre-open states, but the network fragmented upon channel closure. (philipwfowler.me)