KCNQ/M-currents contribute to the resting membrane potential in rat visceral sensory neurons.
The M-current is a slowly activating, non-inactivating potassium current that has been shown to be present in numerous cell types. In this study, KCNQ2, Q3 and Q5, the molecular correlates of M-current in neurons, were identified in the visceral sensory neurons of the nodose ganglia from rats through immunocytochemical studies. All neurons showed expression of each of the three proteins. In voltage clamp studies, the cognition-enhancing drug linopirdine (1-50 microM) and its analogue, XE991 (10 microM), quickly and irreversibly blocked a small, slowly activating current that had kinetic properties similar to KCNQ/M-currents. This current activated between -60 and -55 mV, had a voltage-dependent activation time constant of 208 +/- 12 ms at -20 mV, a deactivation time constant of 165 +/- 24 ms at -50 mV and V1/2 of -24 +/- 2 mV, values which are consistent with previous reports for endogenous M-currents. In current clamp studies, these drugs also led to a depolarization of the resting membrane potential at values as negative as -60 mV. Flupirtine (10-20 microM), an M-current activator, caused a 3-14 mV leftward shift in the current-voltage relationship and also led to a hyperpolarization of resting membrane potential. These data indicate that the M-current is present in nodose neurons, is activated at resting membrane potential and that it is physiologically important in regulating excitability by maintaining cells at negative voltages.
Wladyka
Cynthia L
CL
Rammelkamp Centre for Research and Education R326 MetroHealth Medical Centre, 2500 MetroHealth Drive, Cleveland, OH 44109-1998, USA.
Kunze
Diana L
DL
D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000494:pharmacology; D051656:KCNQ Potassium Channels / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D051658:KCNQ2 Potassium Channel / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D051659:KCNQ3 Potassium Channel / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D008564:Membrane Potentials; D009475:Neurons, Afferent / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D009620:Nodose Ganglion / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D011188:Potassium / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017833:Visceral Afferents / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*
C112297:10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone; D000631:Aminopyridines; D000873:Anthracenes; D007211:Indoles; D051656:KCNQ Potassium Channels; D051658:KCNQ2 Potassium Channel; D051659:KCNQ3 Potassium Channel; C496915:Kcnq2 protein, rat; C496918:Kcnq3 protein, rat; C501028:Kcnq5 protein, rat; D026902:Potassium Channel Blockers; D011725:Pyridines; C061017:linopirdine; C034161:flupirtine; D011188:Potassium