Voltage-gated potassium channel

Voltage-gated potassium channels (VGKCs) are transmembrane channels specific for potassium and sensitive to voltage changes in the cell's membrane potential. During action potentials, they play a crucial role in returning the depolarized cell to a resting state. Classification Alpha subunits Alpha subunits form the actual conductance pore. Based on sequence homology of the hydrophobic transmembrane cores, the alpha subunits of voltage-gated potassium channels are grouped into 12 classes. These are labeled Kvα1-12. The following is a list of the 40 known human voltage-gated potassium channel alpha subunits grouped first according to function and then subgrouped according to the Kv sequence homology classification scheme: Delayed rectifier slowly inactivating or non-inactivating *Kvα1.x - Shaker-related: Kv1.1 (KCNA1), Kv1.2 (KCNA2), Kv1.3 (KCNA3), Kv1.5 (KCNA5), Kv1.6 (KCNA6), Kv1.7 (KCNA7), Kv1.8 (KCNA10) *Kvα2.x - Shab-related: Kv2.1 (KCNB1), Kv2.2 (KCNB

GABA-mediated tonic inhibition differentially modulates gain in functional subtypes of cortical interneurons

Sean Lewis Hill, Steven Petrou, Christian Andreas Rössert, Bas-Jan Zandt

The binding of GABA (gamma-aminobutyric acid) to extrasynaptic GABA(A) receptors generates tonic inhibition that acts as a powerful modulator of cortical network activity. Despite GABA being present throughout the extracellular space of the brain, previous work has shown that GABA may differentially modulate the excitability of neuron subtypes according to variation in chloride gradient. Here, using biophysically detailed neuron models, we predict that tonic inhibition can differentially modulate the excitability of neuron subtypes according to variation in electrophysiological properties. Surprisingly, tonic inhibition increased the responsiveness (or gain) in models with features typical for somatostatin interneurons but decreased gain in models with features typical for parvalbumin interneurons. Patch-clamp recordings from cortical interneurons supported these predictions, and further in silico analysis was then performed to seek a putative mechanism underlying gain modulation. We found that gain modulation in models was dependent upon the magnitude of tonic current generated at depolarized membrane potential-a property associated with outward rectifying GABA(A) receptors. Furthermore, tonic inhibition produced two biophysical changes in models of relevance to neuronal excitability: 1) enhanced action potential repolarization via increased current flow into the dendritic compartment, and 2) reduced activation of voltage-dependent potassium channels. Finally, we show theoretically that reduced potassium channel activation selectively increases gain in models possessing action potential dynamics typical for somatostatin interneurons. Potassium channels in parvalbumin-type models deactivate rapidly and are unavailable for further modulation. These findings show that GABA can differentially modulate interneuron excitability and suggest a mechanism through which this occurs in silico via differences of intrinsic electrophysiological properties.

NATL ACAD SCIENCES2020

A Kinetic Map of the Homomeric Voltage-Gated Potassium Channel (Kv) Family

Valérie Buchillier, Mirjia Herzog, Emmanuelle Logette, Michela Marani, Henry Markram, Enrico Scantamburlo, Valérie Tâche

The voltage-gated potassium (Kv) channels, encoded by 40 genes, repolarize all electrically excitable cells, including plant, cardiac, and neuronal cells. Although these genes were fully sequenced decades ago, a comprehensive kinetic characterization of all Kv channels is still missing, especially near physiological temperature. Here, we present a standardized kinetic map of the 40 homomeric Kv channels systematically characterized at 15, 25, and 35 degrees C. Importantly, the Kv kinetics at 35 degrees C differ significantly from commonly reported kinetics, usually performed at room temperature. We observed voltage-dependent Q(10) for all active Kv channels and inherent heterogeneity in kinetics for some of them. Kinetic properties are consistent across different host cell lines and conserved across mouse, rat, and human. All electrophysiology data from all Kv channels are made available through a public website (Channelpedia). This dataset provides a solid foundation for exploring kinetics of heteromeric channels, roles of auxiliary subunits, kinetic modulation, and for building accurate Kv models.

2019

Kinetics of xylem loading, membrane potential maintenance, and sensitivity of K+-permeable channels to reactive oxygen species: physiological traits that differentiate salinity tolerance between pea and barley

Amandine Massart

Salt sensitive (pea) and salt tolerant (barley) species were used to understand the physiological basis of differential salinity tolerance in crops. Pea plants were much more efficient in restoring otherwise depolarized membrane potential thereby effectively decreasing K+ efflux through depolarization-activated outward rectifying potassium channels. At the same time, pea root apex was 10-fold more sensitive to physiologically relevant H2O2 concentration and accumulated larger amounts of H2O2 under saline conditions. This resulted in a rapid loss of cell viability in the pea root apex. Barley plants rapidly loaded Na+ into the xylem; this increase was only transient, and xylem and leaf Na+ concentration remained at a steady level for weeks. On the contrary, pea plants restricted xylem Na+ loading during the first few days of treatment but failed to prevent shoot Na+ elevation in the long term. It is concluded that superior salinity tolerance of barley plants compared with pea is conferred by at least three different mechanisms: (1) efficient control of xylem Na+ loading; (2) efficient control of H2O2 accumulation and reduced sensitivity of non-selective cation channels to H2O2 in the root apex; and (3) higher energy saving efficiency, with less ATP spent to maintain membrane potential under saline conditions.

Wiley-Blackwell2014

GABA-mediated tonic inhibition differentially modulates gain in functional subtypes of cortical interneurons

Sean Lewis Hill, Steven Petrou, Christian Andreas Rössert, Bas-Jan Zandt

NATL ACAD SCIENCES2020