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J Physiol. 1998 Aug 1;510 ( Pt 3):695-704.

Hyperpolarization-activated cationic currents (Ih) in neurones of the trigeminal mesencephalic nucleus of the rat.

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Department of Pharmacology, School of Medical Sciences, University Walk, University of Bristol, Bristol BS8 1TD, UK.


1. We studied the voltage-dependent current activated by membrane hyperpolarization in sensory proprioceptive trigeminal mesencephalic nucleus (MNV) neurones. 2. Membrane hyperpolarization (from -62 to -132 mV in 10 mV steps) activated slowly activating and non-inactivating inward currents. The hyperpolarization-activated currents could be described by activation curves with a half-maximal activation potential (V ) of -93 mV, slope (k) of 8.4 mV, and maximally activated currents (Imax) of around 1 nA. The reversal potential of the hyperpolarization-activated currents was -57 mV. 3. Extracellular Cs+ blocked hyperpolarization-activated currents rapidly and reversibly in a concentration-dependent manner with an IC50 of 100 microM and Hill slope of 0.8. ZD7288 (1 microM; 4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino) pyridinium chloride), the compound developed as an inhibitor of the cardiac hyperpolarization-activated current (If), also blocked the hyperpolarization-activated currents in MNV neurones. Extracellular Ba2+ (1 mM) did not affect hyperpolarization-activated currents. We tested whether the hyperpolarization-activated currents contribute to the somatic membrane properties of MNV neurones by performing some experiments using current-clamp recording. In such experiments application of Cs+ (1 mM) produced no effect on neuronal resting membrane potentials. 4. During the course of our experiments we noticed that activating ATP-gated non-selective cation channels (P2X receptors) caused an inhibition of Ih associated with a V shift of 10 mV in the hyperpolarizing direction. This P2X receptor-mediated inhibition of Ih was blocked in recordings made with the rapid calcium chelator BAPTA (11 mM) in the pipette solution. 5. We conclude that the current activated by membrane hyperpolarization in MNV neurones is Ih on the basis of its similarity to Ih observed in other neuronal preparations. Activation of Ih can account for the anomalous time-dependent inward rectification that has previously been described in MNV neurones.

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