High impact information on KCNH5

• In qualitative agreement with experiments, the mutations of hEAG1 residues Ser436 and Val437 to the corresponding larger hEAG2 residues (Thr432, Ile433) resulted in reduced sterical fit between the ligand and the binding cavity [1].
• Upon expression in mammalian cells and Xenopus laevis oocytes, we investigated the inhibition of the closely related hEAG1 and hEAG2 channels by agents that have previously been reported to block hERG1 channels [1].
• Heterologous expression of rat eag2 in HEK-293 cells gave rise to a voltage-gated, noninactivating potassium current, active at the cells' resting potential and blocked by low nanomolar concentrations of cytosolic calcium [2].
• The rat eag2 mRNA was predominantly expressed in neural tissue and was not detected in adult skeletal, cardiac, or smooth muscle [2].
• In the Xenopus oocyte expression system the time course of activation was about four times slower and the voltage required for half-maximal subunit activation was about 10 mV greater for hEAG2 channels [3].

Biological context of KCNH5

• In the electrophysiological study, NPMM-differentiated hMSCs expressed two delayed rectifier K(+) currents related to two ether-??-go-go K(+) channels (eag1, eag2), which are fundamental for setting the negative resting potentials required for neuronal survival and basal cell activity [4].
• Coexpression of both isoforms and kinetic analysis of the resulting currents indicated that they can form heteromeric channel complexes in which the slow activation phenotype of hEAG2 is dominant [3].
• Compared with heag1, the conductance-voltage curve for heag2 was shifted to the left, the voltage sensitivity was less, activation kinetics were different, and the sensitivity to terfenadine was lower [5].

Anatomical context of KCNH5

• Heag2 is expressed in the brain, but is also found in a range of tissues including skeletal muscle [5].

Associations of KCNH5 with chemical compounds

• Clofilium inhibited hEAG1 and hERG1 with the same potency, whereas hEAG2 was about 150-fold less sensitive to this antiarrhythmic agent [1].
• We show that not only is the extreme N terminus involved in differences between heag1 and heag2 channels, but also the PAS domain itself [6].

Other interactions of KCNH5

• However, its voltage dependence was smaller and, therefore, hEAG2 channels start to open at more negative voltages than hEAG1 [3].

Analytical, diagnostic and therapeutic context of KCNH5

• We report the molecular cloning from foetal brain of the human potassium channel heag2 [5].

References