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KCNQ/M‐currents contribute to the resting membrane potential in rat visceral sensory neurons
Author(s) -
Wladyka Cynthia L.,
Kunze Diana L.
Publication year - 2006
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2006.113308
Subject(s) - depolarization , membrane potential , hyperpolarization (physics) , current clamp , chemistry , neuroscience , biophysics , voltage clamp , resting potential , electrophysiology , cardiac transient outward potassium current , potassium channel , patch clamp , nodose ganglion , endogeny , activator (genetics) , biology , biochemistry , stimulation , vagus nerve , receptor , stereochemistry , nuclear magnetic resonance spectroscopy
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 μ m ) and its analogue, XE991 (10 μ m ), 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 V 1/2 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 μ m ), 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.