ON THE NATURE OF ANOMALOUS RECTIFICATION IN THALAMOCORTICAL NEURONS OF THE CAT VENTROBASAL THALAMUS IN-VITRO

1. Intracellular sharp electrode current clamp and discontinuous singl e electrode voltage clamp recordings were made from thalamocortical ne urones (n = 57) of the cat ventrobasal thalamus in order to investigat e the mechanisms underlying anomalous rectification. 2. Under current clamp conditions, voltage-current (V-I) relationships in a potential r ange of -55 to -110 mV demonstrated anomalous rectification with two c omponents: fast rectification, which controlled the peak of negative v oltage deviations, and time-dependent rectification. Time-dependent re ctification was apparent as a depolarizing sag generated during the co urse of negative voltage deviations, was first formed at potentials in the range -60 to -70 mV, and was sensitive to 3 mM Cs+ (n = 6). Simil arly: under voltage clamp conditions, instantaneous and steady-state I -V relationships demonstrated anomalous rectification. A slowly activa ting inward current with an activation threshold in the range of -65 t o -70 mV formed time-dependent rectification. This current was sensiti ve to Cs+ (3 mM) (n = 3) and had properties similar to the slow inward mixed cationic current (I-h). 3. ylamino)-1,2-dimethyl-6-(methylamino )-pyrimidinium chloride (ZD 7288) (100-300 mu M) irreversibly blocked time-dependent rectification mediated by I-h (n = 23 oi 25 neurones), and led to a hyperpolarization of the resting membrane potential (6.8 +/- 0.5 mV). In the presence of ZD 7288, V-I and I-V relationships exh ibited fast anomalous rectification, first activated from potential mo re negative than -80 mV. 4. Ba2+ (100 mu M) (n = 8), in the continuous presence of ZD 7288, reversibly linearized peak V-I and instantaneous I-V relationships over a potential range of -70 to -120 mV, and led t o a membrane depolarization (13.3 +/- 4.2 mV) or tonic inward current( 192 +/- 36 pA). 5. The co-application of ZD 7288 and Ba2+ revealed a d epolarizing sag in negative voltage deviations under current clamp con ditions, or a large inward current with kinetics two to three times sl ower than those of I-h under voltage clamp conditions. This novel form of time-dependent rectification was first apparent at potentials more negative than about -85 mV, was sensitive to 5 mM Cs+ (n = 4), and is termed I-h,I-slow. I-h,I-slow tail currents reversed between -65.3 an d -56.6 mV (with potassium acetate electrodes, n = 3) or -57.6 and -50 .3 mV (with KCl electrodes, n = 3). 6. Computer simulations confirmed that the patter n of anomalous rectification in thalamocortical neuron es of the cat ventrobasal thalamus is mediated by the concerted action of I-h and a Ba2+-sensitive current with properties similar to an inw ardly rectifying K+ current (I-KIR).