Contributions of Kv7-mediated potassium current to sub- and suprathreshold responses of rat layer II/III neocortical pyramidal neurons

• Published in: Journal of neurophysiology 2011-10, Vol.106 (4), p.1722-1733
• Main Authors: Guan, D, Higgs, M H, Horton, L R, Spain, W J, Foehring, R C
• Format: Article
• Language: English
• Subjects: Action Potentials - physiology; Animals; Anthracenes - pharmacology; Indoles - pharmacology; Ion Channel Gating - drug effects; Ion Channel Gating - physiology; KCNQ Potassium Channels - drug effects; KCNQ Potassium Channels - physiology; Motor Cortex - cytology; Patch-Clamp Techniques; Potassium - physiology; Potassium Channel Blockers - pharmacology; Pyramidal Cells - drug effects; Pyramidal Cells - physiology; Pyridines - pharmacology; Rats; Rats, Sprague-Dawley; Sensory Thresholds - physiology; Somatosensory Cortex - cytology; Subliminal Stimulation
• ISSN: 0022-3077; 1522-1598
• DOI: 10.1152/jn.00211.2011

After block of Kv1- and Kv2-mediated K(+) currents in acutely dissociated neocortical pyramidal neurons from layers II/III of rat somatosensory and motor cortex, the remaining current is slowly activating and persistent. We used whole cell voltage clamp to show that the Kv7 blockers linopirdine and XE-991 blocked a current with similar kinetics to the current remaining after combined block of Kv1 and Kv2 channels. This current was sensitive to low doses of linopirdine and activated more slowly and at more negative potentials than Kv1- or Kv2-mediated current. The Kv7-mediated current decreased in amplitude with time in whole cell recordings, but in most cells the current was stable for several minutes. Current in response to a traditional M-current protocol was blocked by muscarine, linopirdine, and XE-991. Whole cell slice recordings revealed that the Q₁₀ for channel deactivation was ∼2.5. Sharp electrode current-clamp recordings from adult pyramidal cells demonstrated that block of Kv7-mediated current with XE-991 reduced rheobase, shortened the latency to firing to near rheobase current, induced more regular firing at low current intensity, and increased the rate of firing to a given current injection. XE-991 did not affect single action potentials or spike frequency adaptation. Application of XE-991 also eliminated subthreshold voltage oscillations and increased gain for low-frequency inputs (