On the nature of anomalous rectification in thalamocortical neurones of the cat ventrobasal thalamus in vitro

Abstract

1. Intracellular sharp electrode current clamp and discontinuous single electrode voltage clamp recordings were made from thalamocortical neurones (n = 57) of the cat ventrobasal thalamus in order to investigate the mechanism underlying anomalous rectification. 2. Under current clamp conditions, voltage-current (V-I) relationships in a potential range of -55 to -110 mV demonstrated anomalous rectification with two components: fast rectification, which controlled the peak of negative voltage deviations, and time-dependent rectification. Time-dependent rectification was apparent as a depolarizing sag generated during the course 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). Similarly, under voltage clamp conditions, instantaneous and steady-state I-V relationships demonstrated anomalous rectification. A slowly activating inward current with an activation threshold in the range of -65 to -70 mV formed time-dependent rectification. This current was sensitive to Cs+ (3 mM) (n = 3) and had properties similar to the slow inward mixed cationic current (Ih). 3. 4-(N-Ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino)-pyrimidinium++ + chloride (ZD 7288) (100-300 microM) irreversibly blocked time-dependent rectification mediated by Ih (n = 23 of 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, exhibited fast anomalous rectification, first activated from potential more negative than -80 mV. 4. Ba2+ (100 microM) (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 to 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 depolarizing sag in negative voltage deviations under current clamp conditions, or a large inward current with kinetics two to three times slower than those of Ih 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 Ih,slow. Ih,slow tail currents reversed between -65.3 and -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 pattern of anomalous rectification in thalamocortical neurones of the cat ventrobasal thalamus is mediated by the concerted action of Ih and a Ba(2+)-sensitive current with properties similar to an inwardly rectifying K+ current (IKIR).

Morphology and membrane properties of neurones in the cat ventrobasal thalamus in Vitro

“…The aim of the present study, therefore, was to examine the membrane and firing properties of neurones in the cat VB thalamus and, by ascertaining their morphology, to compare these properties for small and large TC neurones. The findings presented here, and in the accompanying papers (Williams, T oth, Turner, Hughes & Crunelli, 1997a;Williams, Turner, Hughes & Crunelli, 1997b), clearly indicate the presence of important differences and similarities with other thalamic nuclei and between large and small TC neurones within the VB. Some of these results have been published in preliminary form (Turner, Anderson & Crunelli, 1994).…”

“…There was, however, a positive correlation between the size of the depolarizing sag and the peak of the voltage response for each of the non-oscillating neurones (P < 0·05-0·01, n = 28) ( Table 2). A detailed analysis of the properties of inward rectification in TC neurones of the cat VB thalamus is presented in the accompanying paper (Williams et al 1997b). …”

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

“…However, in other neurones Ih can contribute substantially to the resting and active properties of neurones, e.g. thalamic relay neurones (McCormick & Pape, 1990), hippocampal neurones (Maccaferri et al 1993;Gasparini & DiFrancesco, 1997), neurones of the basolateral amygdala (Womble & Moises, 1993) and ventrobasal thalamic neurones (Williams et al 1997). The reasons why Ih is active at rest in some neurone types and not in others is unclear at present.…”

Properties and Role of I h in the Pacing of Subthreshold Oscillations in Entorhinal Cortex Layer II Neurons

“…It was dose dependent and ranged from 60 to 75% for a concentration of 2 mM Cs ϩ (n ϭ 5) that produced close to maximal effects. Given that Cs ϩ produced only a partial block of I h in the SCs, we assessed the effects of the novel bradycardic agent ZD7288, which has been reported to be a potent blocker of I h in other cells (BoSmith et al 1993;Harris and Constanti 1995;Maccaferri and McBain 1996;Williams et al 1997). As illustrated in Fig.…”