Use Dependent Attenuation of Rat HCN1-Mediated Ih in Intact HEK293 Cells

作者: Lennart Barthel , Olivia Reetz , Ulf Strauss

DOI: 10.1159/000445566

关键词:

摘要: Background/Aims: Cationic currents (Ih) through the fast activating and relatively cAMP insensitive subtype of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, HCN1, are limited by cytosolic factors in mammalian cells. This HCN1 break is boosted changes membrane voltage that not characterized on a biophysical level, yet. Methods: We overexpressed rat (r)HCN1 human embryonic kidney cells (HEK293) recorded pharmacologically isolated Ih cell-attached or whole-cell mode patch-clamp technique. Results: Recurring activation rHCN1 reduced slowed intact HEK293 (cell-attached mode). On contrary, sustained disruption intracellular content (whole-cell mode) ceased activity dependence partially enables dependent hysteresis. The induced attenuation was independent main external cation, depended number previous forced activations - at least part due to shift towards hyperpolarization as estimated an adapted tail current analysis. Intracellular elevation could reverse Ih. Conclusion: Reduction mediated use may involve coupling sensor pore.

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