The Journal of Neurophysiology Vol. 79 No. 6 June 1998, pp. 3111-3126
Copyright ©1998 The American Physiological Society

Voltage-Clamp Analysis and Computer Simulation of a Novel Cesium-Resistant A-Current in Guinea Pig Laterodorsal Tegmental Neurons

Russell M. Sanchez, Alisa Surkis, and Christopher S. Leonard

Department of Physiology, New York Medical College, Valhalla, New York 10595

Sanchez, Russell M., Alisa Surkis, and Christopher S. Leonard. Voltage-clamp analysis and computer simulation of a novel cesium-resistant A-current in guinea pig laterodorsal tegmental neurons. J. Neurophysiol. 79: 3111-3126, 1998. Increased firing of cholinergic neurons of the laterodorsal tegmental nucleus (LDT) plays a critical role in generating the behavioral states of arousal and rapid eye movement sleep. The majority of these neurons exhibit a prominent transient potassium current (I_A) that shapes firing but the properties of which have not been examined in detail. Although I_A has been reported to be blocked by intracellular cesium, the I_A in LDT neurons appeared resistant to intracellular cesium. The present study compared the properties of this cesium-resistant current to those typically ascribed to I_A. Whole cell recordings were obtained from LDT neurons (n = 67) in brain slices with potassium- or cesium-containing pipette solutions. A transient current was observed in cells dialyzed with each solution (KGluc-85%; CsGluc-79%). However, in cesium-dialyzed neurons, the transient current was inward at test potentials negative to about 35 mV. Extracellular 4-aminopyridine (4-AP; 2-5 mM) blocked both inward and outward current, suggesting the inward current was reversed I_A rather than an unmasked transient calcium current as previously suggested. This conclusion was supported by increasing [K]_o from 5 to 15 mM, which shifted the reversal potential positively for both inward and outward current (+17.89 ± 0.41 mV; mean ± SE). Moreover, recovery from inactivation was rapid ( = 15.5 ± 4 ms; n = 4), as reported for I_A, and both inward and outward transient current persisted in calcium-free solution [0 calcium/4 mM ethylene glycol-bis(-aminoethyl ether)-N,N,N',N'-tetraacetic acid; n = 4] and during cadmium-blockade of calcium currents (n = 3). Finally, the transient current was blocked by intracellular 4-AP indicating that adequate dialysis occurred during the recordings. Thus the Cs-resistant current is a subthreshold I_A. We also estimated the voltage-dependence of activation (V_1/2 = 45.8 ± 2 mV, k = 5.21 ± 0.62 mV, n = 6) and inactivation (V_1/2 = 59.0 ± 2.38 mV, k = 5.4 ± 0.49 mV, n = 3) of this current. Computer simulations using a morphologically accurate model cell indicated that except for the extreme case of only distal A-channels and a high intracellular resistivity, our parameter estimates were good approximations. In conclusion, guinea pig LDT neurons express subthreshold A-channels that are resistant to intracellular cesium ions. This suggests that these channels differ fundamentally in their ion permeation mechanism from those previously studied. It remains to be determined if Cs⁺ resistance is common among brain A-channels or if this property is conferred by known A-channel subunits.

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