Muscarinic receptors regulate two different calcium-dependent non-selective cation currents in rat prefrontal cortex

Authors

  • Samir Haj-Dahmane,

    1. Department of Psychiatry and Behavioural Neurosciences, Wayne State University School of Medicine, 540 E. Canfield, Detroit, MI 48201, USA
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  • Rodrigo Andrade

    1. Cellular and Clinical Neurobiology Training Program, Wayne State University School of Medicine, 540 E. Canfield, Detroit, MI 48201, USA
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R. Anrade, as above.
E-mail: ranrade@med.wayne.edu

Abstract

Pyramidal neurons of layer V in rat prefrontal cortex display a prominent fast afterdepolarization (fADP) and a muscarinic-induced slow afterdepolarization (sADP). We have shown previously that both of these ADPs are produced by the activation of calcium-dependent non-selective cation currents. In the present report we examine whether they represent two distinct currents. In most pyramidal neurons recorded with caesium gluconate-based intracellular solution, a calcium spike is followed by a fast decaying inward aftercurrent (IfADP). The decay of IfADP is monoexponential with a time constant (τ) of ≈ 35 ms. Administration of carbachol (10–30 μm) increases the time constant of this decay by ≈ 80% and induces the appearance of a much slower inward aftercurrent (IsADP). IfADP recorded in control conditions and in the presence of carbachol increases linearly with membrane hyperpolarization. In contrast, the carbachol-induced IsADP decreases with membrane hyperpolarization. When the sodium driving force across the cell membrane was reduced, IfADP was found to reverse at around −40 mV whereas IsADP remain inward over the same voltage range tested. Finally, bath administration of flufenamic acid (100 μm–1 mm) selectively blocks the carbachol-induced IsADP without a significant effect on the amplitude of IfADP. These differences in the electrical and pharmacological properties of IfADP and IsADP suggest that they were mediated by two distinct non-selective cation currents.

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