| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Received May 10, 2006
Revised June 14, 2006
Accepted after revision June 14, 2006
1 Case Western Reserve University
2 MetroHealth/Case Western Reserve University
* To whom correspondence should be addressed. E-mail: dkunze{at}metrohealth.org.
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 (1-50µM) and its analogue, XE991 (10µM), quickly and irreversibly blocked a small, slowly activating current that had kinetic properties similar to KCNQ/M-currents. This current activated between -60 and -55mV, had a voltage-dependent activation time constant of 208 ± 12ms at -20mV, a deactivation time constant of 165 ± 24 ms at -50mV and V1/2 of -24 ± 2mV, 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 -60mV. Flupirtine (10-20µM), an M-current activator, caused a 3-14mV 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.
This article has been cited by other articles:
|
|
 |
|
  M. Bal, J. Zhang, O. Zaika, C. C. Hernandez, and M. S. Shapiro Homomeric and Heteromeric Assembly of KCNQ (Kv7) K+ Channels Assayed by Total Internal Reflection Fluorescence/Fluorescence Resonance Energy Transfer and Patch Clamp Analysis J. Biol. Chem., November 7, 2008; 283(45): 30668 - 30676. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. R. Mackie and K. L. Byron Cardiovascular KCNQ (Kv7) Potassium Channels: Physiological Regulators and New Targets for Therapeutic Intervention Mol. Pharmacol., November 1, 2008; 74(5): 1171 - 1179. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. B. Sattler, S. K. Williams, C. Neusch, M. Otto, J. R. Pehlke, M. Bahr, and R. Diem Flupirtine as Neuroprotective Add-On Therapy in Autoimmune Optic Neuritis Am. J. Pathol., November 1, 2008; 173(5): 1496 - 1507. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. C. Hernandez, O. Zaika, G. P. Tolstykh, and M. S. Shapiro Regulation of neural KCNQ channels: signalling pathways, structural motifs and functional implications J. Physiol., April 1, 2008; 586(7): 1811 - 1821. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Wladyka, B. Feng, P. A. Glazebrook, J. H. Schild, and D. L. Kunze The KCNQ/M-current modulates arterial baroreceptor function at the sensory terminal in rats J. Physiol., February 1, 2008; 586(3): 795 - 802. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Snitsarev, C. A. Whiteis, M. W. Chapleau, and F. M. Abboud Mechano- and chemosensitivity of rat nodose neurones - selective excitatory effects of prostacyclin J. Physiol., July 1, 2007; 582(1): 177 - 194. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
