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

Authors

  • Stephen R. Williams,

    1. Physiology Unit, School of Molecular and Medical Biosciences, University of Wales Cardiff Museum Avenue, Cardiff, CF1 1SS, UK
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  • Jonathan P. Turner,

    1. Physiology Unit, School of Molecular and Medical Biosciences, University of Wales Cardiff Museum Avenue, Cardiff, CF1 1SS, UK
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  • Stuart W. Hughes,

    1. Physiology Unit, School of Molecular and Medical Biosciences, University of Wales Cardiff Museum Avenue, Cardiff, CF1 1SS, UK
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  • Vincenzo Crunelli

    Corresponding author
    1. Physiology Unit, School of Molecular and Medical Biosciences, University of Wales Cardiff Museum Avenue, Cardiff, CF1 1SS, UK
    • To whom correspondence should be addressed.

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  • Authors’ present addresses
    S.R. Williams: Reed Neurological Research Center, UCLA School of Medicine, Los Angeles CA 90024, USA.
    J. P. Turner: Department of Visual Science, Institute of Opthalmology, London EC1V 9EL, UK.

  • Author's email address
    V. Cruneli: crunelli@cardiff.ac.uk

Abstract

  • 1Intracellular 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 mechanisms underlying anomalous rectification.
  • 2Under 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).
  • 34-(N-Ethyl-N-phenylamino)-l,2-dimethyl-6-(methylamino)-pyrimidinium chloride (ZD7288) (100–300 μm) 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.
  • 4Ba2+ (100 μm) (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).
  • 5The 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).
  • 6Computer 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 Ba2+ -sensitive current with properties similar to an inwardly rectifying K+ current (IKIR).

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