https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:18946 + currents could be a key model component requiring improvement to produce the longer-lasting bursting APs. Of the delayed rectifying K⁺ currents family it is of interest that KCNQ and hERG channels have been reported to be gestationally regulated in the uterus. These currents exhibit features similar to the broadly defined uterine I_K1 of the original mathematical model. We thus formulated new quantitative descriptions for several I_KCNQ and I_hERG. Incorporation of these currents into the uterine cell model enabled simulations of the long-lasting bursting APs. Moreover, we used this modified model to simulate the effects of different contributions of I_KCNQ and I_hERG on AP form. Our findings suggest that the alterations in expression of hERG and KCNQ channels can potentially provide a mechanism for fine tuning of AP forms that lends a malleability for changing between plateau-like and long-lasting bursting-type APs as uterine cells prepare for parturition.]]> Wed 11 Apr 2018 09:53:37 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:20078 Sat 24 Mar 2018 08:00:08 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:27526 Sat 24 Mar 2018 07:28:58 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:46291 2+-activated K⁺ channel, K_Ca1.1, and lies within a linkage interval for atrial fibrillation (AF). Insights into the cardiac functions of K_Ca1.1 are limited, and KCNMA1 has not been investigated as an AF candidate gene. Methods; The KCNMA1 gene was sequenced in 118 patients with familial AF. The role of K_Ca1.1 in normal cardiac structure and function was evaluated in humans, mice, zebrafish, and fly. A novel KCNMA1 variant was functionally characterized.Results: A complex KCNMA1 variant was identified in 1 kindred with AF. To evaluate potential disease mechanisms, we first evaluated the distribution of K_Ca1.1 in normal hearts using immunostaining and immunogold electron microscopy. K_Ca1.1 was seen throughout the atria and ventricles in humans and mice, with strong expression in the sinus node. In an ex vivo murine sinoatrial node preparation, addition of the K_Ca1.1 antagonist, paxilline, blunted the increase in beating rate induced by adrenergic receptor stimulation. Knockdown of the K_Ca1.1 ortholog, kcnma1b, in zebrafish embryos resulted in sinus bradycardia with dilatation and reduced contraction of the atrium and ventricle. Genetic inactivation of the Drosophila K_Ca1.1 ortholog, slo, systemically or in adult stages, also slowed the heartbeat and produced fibrillatory cardiac contractions. Electrophysiological characterization of slo-deficient flies revealed bursts of action potentials, reflecting increased events of fibrillatory arrhythmias. Flies with cardiac-specific overexpression of the human KCNMA1 mutant also showed increased heart period and bursts of action potentials, similar to the K_Ca1.1 loss-of-function models. Conclusions: Our data point to a highly conserved role of K_Ca1.1 in sinus node function in humans, mice, zebrafish, and fly and suggest that K_Ca1.1 loss of function may predispose to AF.]]> Mon 14 Nov 2022 16:44:58 AEDT ]]>