Hyperpolarization‐activated cationic currents (I_h) in neurones of the trigeminal mesencephalic nucleus of the rat

Abstract

We studied the voltage‐dependent current activated by membrane hyperpolarization in sensory proprioceptive trigeminal mesencephalic nucleus (MNV) neurones. 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 (V½) 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. Extracellular Cs+ blocked hyperpolarization‐activated currents rapidly and reversibly in a concentration‐dependent manner with an IC50 of 100 μM and Hill slope of 0.8. ZD7288 (1 μM; 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. 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 V½ 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. 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.

Mammalian Retinal Bipolar Cells Express Inwardly Rectifying K+ Currents (IKir) With a Different Distribution Than That of Ih

“…Second, the current was blocked by ZD 7288, a selective blocker of I h (BoSmith et al 1993;Harris and Constanti 1995). Furthermore, Ba 2ϩ had no effect on this current, consistent with the property of I h reported in many other systems (Khakh and Henderson 1998;Lamas 1998;Tabata and Isida 1996). Although the expression of I h in mammalian bipolar cells was expected since I h has been previously reported in rat RBCs (Karschin and Wässle 1990), the distinct biophysical and pharmacological properties of the two components of the hyperpolarization-activated currents shown in this study clearly demonstrate that bipolar cells of different subtypes differentially express two types of hyperpolarizationactivated currents (see DISCUSSION below).…”

Development of Inward Rectification and Control of Membrane Excitability in Mesencephalic V Neurons

“…Hyperpolarizing current pulses (0.2-0.5 nA) consistently produced voltage-and time-dependent depolarizing sag during current-clamp recording in normal ACSF, indicative of an underlying inward rectifying I h described previously in Mes V neurons (Khakh and Henderson 1998) (Fig. 1A).…”

“…Inward rectification in response to membrane hyperpolarization is a common membrane property of many central and peripheral neurons, including Mes V neurons (Del Negro and Chandler 1997;Khakh and Henderson 1998). Typically, a nonselective cationic current, I h , and a fast K ϩ selective current, I KIR , are the basis for this property (Hogg et al 2001;Kjaerulff and Kiehn 2001;Travagli and Gillis 1994;Womble and Moises 1993).…”

Participation of Sodium Currents in Burst Generation and Control of Membrane Excitability in Mesencephalic Trigeminal Neurons

“…Mesencephalic V neurons exhibit prominent I h current (Khakh and Henderson, 1998;Tanaka et al, 2003) and both lowand high-threshold calcium currents (our unpublished observations) that could participate in production of net inward current to drive spike activity during burst discharge. Using the action potential-clamp method, we determined the time course and extent of current flow through those channels.…”