Protein kinase C activation inhibits rat and human hyperpolarization activated cyclic nucleotide gated channel (HCN)1--mediated current in mammalian cells.

摘要: Background/Aims: Hyperpolarization activated cyclic nucleotide gated 1 (HCN1) channels determine neuronal excitability in several brain regions. In contrast to HCN2 and HCN4, HCN1 is less sensitive cAMP the number of other known modulators limited. One those, protein kinase C (PKC), showed opposing effects on mouse expressed Xenopus oocytes. Methods: order study PKC mediated currents a mammalian environment we rat or human embryonic kidney (HEK293) cells murine neuroblastoma (N1E-115) cells. We recorded resulting Ih before during application membrane permeable non-metabolizable PKC-activator 4βPMA cell-attached mode patch-clamp technique, leaving intracellular intact. Results: reduced maximal about 60-70 % slowed its activation, but left voltage sensitivity unchanged. The effect was neither due species-related differences nor restricted HEK293 cells, because it comparable for N1E-115 However, pre-treatment with blocker GF109203X abolished induced changes. Disrupting by recording whole-cell drastically effect. Conclusion: activation reduces slows non-neuronal transfected if content remains