| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Physiology, Emory University, Atlanta, Georgia, USA
2 Medicine/ Cardiology, University of Louisville, Louisville, Kentucky, USA
3 Pediatrics, Emory University, Atlanta, Georgia, USA
* To whom correspondence should be addressed. E-mail: aruni{at}louisville.edu.
The activity of the voltage-sensitive K+ channels (Kv) varies as a function of the intracellular redox state and metabolism and several Kv channels act as oxygen sensors. However, the mechanisms underlying the metabolic and redox regulation of these channels remain unclear. In this study we investigated the regulation of Kv channels by pyridine nucleotides. Heterologous expression of Kv
1.5 in COS-7 cells led to the appearance of non-inactivating currents. Inclusion of 0.1 to 1 mM NAD+ or 0.03 to 0.5 mM NADP+ in the internal solution of the patch pipette did not affect Kv currents. However, 0.5 and 1 mM NAD+ and 0.1 and 0.5 mM NADP+ prevented inactivation of Kv currents in cells transfected with Kv1.5 and Kv
1.3 and shifted the voltage-dependence of activation to depolarized potential. The Kv-dependent inactivation of Kv currents was also decreased by internal pipette perfusion of the cell with 1 mM NAD+. The Kv1.5-Kv1.3 currents were unaffected by the internal application of 0.1 mM NADPH or 0.1 or 1 mM NADH. Excised inside-out patches from cells expressing Kv1.5-Kv1.3 showed transient single channel activity. The mean open time and the opening probability of these currents were increased by the inclusion of 1 mM NAD+ in the perfusate. These results suggest that NAD[P]+ prevents Kv-mediated inactivation of Kv currents and provide a novel mechanism by which pyridine nucleotides could regulate specific K+ currents as a function of the cellular redox state (NAD[P]H/NAD[P]+ ratio).
This article has been cited by other articles:
|
|
 |
|
  M. Liu, S. Sanyal, G. Gao, I. S. Gurung, X. Zhu, G. Gaconnet, L. J. Kerchner, L. L. Shang, C. L.-H. Huang, A. Grace, et al. Cardiac Na+ Current Regulation by Pyridine Nucleotides Circ. Res., October 9, 2009; 105(8): 737 - 745. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. J. Tamsett, K. E. Picchione, and A. Bhattacharjee NAD+ Activates KNa Channels in Dorsal Root Ganglion Neurons J. Neurosci., April 22, 2009; 29(16): 5127 - 5134. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Li, S. Y. Um, and T. V. Mcdonald Voltage-Gated Potassium Channels: Regulation by Accessory Subunits Neuroscientist, June 1, 2006; 12(3): 199 - 210. [Abstract] [PDF]
|
|
|
|
 |
|
 P. E MacDonald, J. W Joseph, and P. Rorsman Glucose-sensing mechanisms in pancreatic {beta}-cells Phil Trans R Soc B, December 29, 2005; 360(1464): 2211 - 2225. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. K. Weir, J. Lopez-Barneo, K. J. Buckler, and S. L. Archer Acute Oxygen-Sensing Mechanisms. N. Engl. J. Med., November 10, 2005; 353(19): 2042 - 2055. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
