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NEUROSCIENCE |
1 Rammelkamp Centre for Research and Education, MetroHealth Medical Centre and Department of Neurosciences, Case Western Reserve University, Cleveland, OH 44109, USA
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 (150 µM) and its analogue, XE991 (10 µM), 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 (1020 µM), an M-current activator, caused a 314 mV leftward shift in the currentvoltage 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.
(Received 10 May 2006;
accepted after revision 14 June 2006;
first published online 15 June 2006)
Corresponding author D. L. Kunze: Rammelkamp Centre for Research and Education R326 MetroHealth Medical Centre, 2500 MetroHealth Drive, Cleveland, OH 44109-1998, USA. Email: dkunze{at}metrohealth.org
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