Muscarinic receptors regulate two different calcium-dependent non-selective cation currents in rat prefrontal cortex.
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.
Haj-Dahmane
S
S
Department of Psychiatry and Behaviroural Neurosciences, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Andrade
R
R
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002217:Carbachol / Q000494:pharmacology; D002412:Cations / Q000378:metabolism*; D004553:Electric Conductivity; D004594:Electrophysiology; D066298:In Vitro Techniques; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000502:physiology; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*
D002412:Cations; D018721:Muscarinic Agonists; D011976:Receptors, Muscarinic; D002217:Carbachol; D002118:Calcium