A lower X-gate in TASK channels traps inhibitors within the vestibule.

TWIK-related acid-sensitive potassium (TASK) channels-members of the two pore domain potassium (K) channel family-are found in neurons, cardiomyocytes and vascular smooth muscle cells, where they are involved in the regulation of heart rate, pulmonary artery tone, sleep/wake cycles and responses to volatile anaesthetics. K channels regulate the resting membrane potential, providing background K currents controlled by numerous physiological stimuli. Unlike other K channels, TASK channels are able to bind inhibitors with high affinity, exceptional selectivity and very slow compound washout rates.

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

Background: Inherited forms of sinus node dysfunction (SND) clinically include bradycardia, sinus arrest, and chronotropic incompetence and may serve as disease models to understand sinus node physiology and impulse generation. Recently, a gain-of-function mutation in the G-protein gene GNB2 led to enhanced activation of the GIRK (G-protein activated inwardly rectifying K channel). Thus, human cardiac GIRK channels are important for heart rate regulation and subsequently, genes encoding their subunits Kir3.

Tranexamic Acid Prophylaxis in Hip and Knee Joint Replacement.

Background: The antifibrinolytic agent tranexamic acid (TXA) is widely used for the prevention and treatment of hyperfibrinolytic states, such as in severe polytrauma. It can also be used for the systemic prevention of hemorrhage in elective orthopedic procedures. In this review, we assess the efficacy and risks of the prophylactic administration of tranexamic acid before major endoprosthetic surgery of the hip and knee.

Functional mutagenesis screens reveal the 'cap structure' formation in disulfide-bridge free TASK channels.

Two-pore-domain potassium (K2P) channels have a large extracellular cap structure formed by two M1-P1 linkers, containing a cysteine for dimerization. However, this cysteine is not present in the TASK-1/3/5 subfamily. The functional role of the cap is poorly understood and it remained unclear whether K2P channels assemble in the domain-swapped orientation or not.