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

Eur J Neurosci. 1999 Jun;11(6):1973-80. doi: 10.1046/j.1460-9568.1999.00612.x.


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 (t) of approximately 35 ms. Administration of carbachol (10-30 microm) increases the time constant of this decay by approximately 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 microm-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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcium / physiology*
  • Carbachol / pharmacology
  • Cations / metabolism*
  • Electric Conductivity
  • Electrophysiology
  • In Vitro Techniques
  • Male
  • Muscarinic Agonists / pharmacology
  • Prefrontal Cortex / metabolism
  • Prefrontal Cortex / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Reaction Time / physiology
  • Receptors, Muscarinic / drug effects
  • Receptors, Muscarinic / physiology*


  • Cations
  • Muscarinic Agonists
  • Receptors, Muscarinic
  • Carbachol
  • Calcium