A novel slow hyperpolarization‐activated potassium current ( I K(SHA) ) from a mouse hippocampal cell line

1 A slow hyperpolarization‐activated inwardly rectifying K + current ( I K(SHA) ) with novel characteristics was identified from the mouse embryonic hippocampus x neuroblastoma cell line HN9.10e. 2 The non‐inactivating current activated negative to a membrane potential of −80 mV with slow and complex activation kinetics ( τ act ≈ 1–7 s) and a characteristic delay of 1–10 s (−80 to −140 mV) that was linearly dependent on the membrane potential. 3 Tail currents and instantaneous open channel currents determined through fast voltage ramps reversed at the K + equilibrium potential ( E K ) indicating that primarily K + , but not Na + , permeated the channels. 4 IK(SHA) was unaffected by altering the intracellular Ca 2+ concentration between ∼0 and 10 μ m , but was susceptible to block by 5 m m extracellular Ca 2+ , Ba 2+ ( K 1 = 0.42 m m ), and Cs + ( K 1 = 2.77 m m ) 5 In cells stably transformed with M2 muscarinic receptors, I K(SHA) was rapidly, but reversibly, suppressed by application of micromolar concentrations of muscarine. 6 At the single channel level K(SHA) channel openings were observed with the characteristic delay upon membrane hyperpolarization. Analysis of unitary currents revealed an inwardly rectifying I–V profile and a channel slope conductance of 7 pS. Channel activity persisted in the inside‐out configuration for many minutes. 7 It is concluded that I K(SHA) m HN9.10e cells represents a novel K + current, which is activated upon membrane hyperpolarization. It is functionally different from both classic inwardly rectifying I kir currents and other cationic hyperpolarization‐activated 7 H currents that have been previously described in neuronal or glial cells.