Arrhythmogenic mechanism of a novel ryanodine receptor mutation underlying sudden cardiac death.

Aims: The ryanodine receptor 2 (RyR2) is essential for cardiac muscle excitation-contraction coupling; dysfunctional RyR2 participates in the development of inherited arrhythmogenic cardiac disease. In this study, a novel RyR2 mutation A690E is identified from a patient with family inheritance of sudden cardiac death, and we aimed to investigate the pathogenic basis of the mutation.

Methods And Results: We generated a mouse model that carried the A690E mutation.

The Effect of TWIK-1 Two Pore Potassium Channels on Cardiomyocytes in Low Extracellular Potassium Conditions.

Backgroound: At low extracellular potassium ([K+]e) conditions, human cardiomyocytes can depolarize to -40 mV. This is closely related to hypokalemia-induced fatal cardiac arrhythmia. The underlying mechanism, however, is still not well understood.

K2P1 leak cation channels contribute to ventricular ectopic beats and sudden death under hypokalemia.

Hypokalemia causes ectopic heartbeats, but the mechanisms underlying such cardiac arrhythmias are not understood. In reduced serum K concentrations that occur under hypokalemia, K2P1 two-pore domain K channels change ion selectivity and switch to conduct inward leak cation currents, which cause aberrant depolarization of resting potential and induce spontaneous action potential of human cardiomyocytes. K2P1 is expressed in the human heart but not in mouse hearts.

Effect of inward rectifier potassium 2.1 channel on the osteogenic differentiation of human dental follicle cells and its mechanism.

Objectives: This study aims to explore the effect of inward rectifier potassium (Kir) 2.1 channel on the osteogenic differentiation of human dental follicle cells (hDFCs) and its mechanism.

Methods: hDFCs were isolated and cultured, and their source was verified by flow cytometry.

Enrichment differentiation of human induced pluripotent stem cells into sinoatrial node-like cells by combined modulation of BMP, FGF, and RA signaling pathways.

Background: Biological pacemakers derived from pluripotent stem cell (PSC) have been considered as a potential therapeutic surrogate for sick sinus syndrome. So it is essential to develop highly efficient strategies for enrichment of sinoatrial node-like cells (SANLCs) as seed cells for biological pacemakers. It has been reported that BMP, FGF, and RA signaling pathways are involved in specification of different cardiomyocyte subtypes, pacemaker, ventricular, and atrial cells.

[Effect of calcium on proliferation, migration and osteogenic differentiation of human dental follicle cells].

Purpose: To determine the role of Ca in proliferation,migration and osteogenic differentiation of human dental follicle cells(hDFCs).

Methods: hDFCs were isolated and cultured. The source of hDFCs was detected by immunofluorescence staining.

Kir2 inward rectification-controlled precise and dynamic balances between Kir2 and HCN currents initiate pacemaking activity.

Spontaneous rhythmic action potential or pacemaking activity of pacemaker cells controls rhythmic signaling such as heartbeat. The mechanism underlying the origin of pacemaking activity is not well understood. In this study, we created human embryonic kidney (HEK) 293 cells that show pacemaking activity through heterologous expression of strong inward rectifier K subfamily 2 isoform 1 (Kir2.

Kir2.1 channels set two levels of resting membrane potential with inward rectification.

Strong inward rectifier K channels (Kir2.1) mediate background K currents primarily responsible for maintenance of resting membrane potential. Multiple types of cells exhibit two levels of resting membrane potential.

Kir2.1 and K2P1 channels reconstitute two levels of resting membrane potential in cardiomyocytes.

Key Points: Outward and inward background currents across the cell membrane balance, determining resting membrane potential. Inward rectifier K channel subfamily 2 (Kir2) channels primarily maintain the resting membrane potential of cardiomyocytes. Human cardiomyocytes exhibit two levels of resting membrane potential at subphysiological extracellular K concentrations or pathological hypokalaemia, however, the underlying mechanism is unclear.

Classification of 2-pore domain potassium channels based on rectification under quasi-physiological ionic conditions.

It is generally expected that 2-pore domain K(+) (K2P) channels are open or outward rectifiers in asymmetric physiological K(+) gradients, following the Goldman-Hodgkin-Katz (GHK) current equation. Although cloned K2P channels have been extensively studied, their current-voltage (I-V) relationships are not precisely characterized and previous definitions are contradictory. Here we study all the functional channels from 6 mammalian K2P subfamilies in transfected Chinese hamster ovary cells with patch-clamp technique, and examine whether their I-V relationships are described by the GHK current equation.