HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Harvey, J. Articles by Ashford, M. L. J. Search for Related Content PubMed PubMed Citation Articles by Harvey, J. Articles by Ashford, M. L. J.

Leptin activation of ATP-sensitive K⁺ (K_ATP) channels in rat CRI-G1 insulinoma cells involves disruption of the actin cytoskeleton

J. Harvey, S. C. Hardy, A. J. Irving and M. L. J. Ashford

1. The role of the cytoskeleton in leptin-induced activation of ATP-sensitive K⁺ (K_ATP) channels was examined in rat CRI-G1 insulin-secreting cells using patch clamp and fluorescence imaging techniques.

2. In whole cell recordings, dialysis with the actin filament stabiliser phalloidin (10 µM) prevented K_ATP channel activation by leptin.

3. Application of the actin filament destabilising agents deoxyribonuclease type 1 (DNase 1; 50 µg ml^-1) or cytochalasin B (10 µM) to intact cells or inside-out membrane patches also increased K_ATP channel activity in a phalloidin-dependent manner.

4. The anti-microtubule agents nocodazole (10 µM) and colchicine (100 µM) had no effect on K_ATP channel activity.

5. Fluorescence staining of the cells with rhodamine-conjugated phalloidin revealed rapid disassembly of actin filaments by cytochalasin B and leptin, the latter action being prevented by the phosphoinositide 3 (PI 3)-kinase inhibitor LY 294002.

6. Activation of K_ATP channels by the PI 3-kinase product phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P₃) was also prevented by phalloidin. This is consistent with the notion that leptin activates K_ATP channels in these cells by an increase in PtdIns(3,4,5)P₃ or a similar 3-phosphorylated phosphoinositol lipid, resulting in actin filament disruption.

This article has been cited by other articles:

				L. Tian, L. Chen, H. McClafferty, C. A. Sailer, P. Ruth, H.-G. Knaus, and M. J. Shipston A noncanonical SH3 domain binding motif links BK channels to the actin cytoskeleton via the SH3 adapter cortactin FASEB J, December 1, 2006; 20(14): 2588 - 2590. [Abstract] [Full Text] [PDF]

				K. W. Williams and B. N. Smith Rapid inhibition of neural excitability in the nucleus tractus solitarii by leptin: implications for ingestive behaviour J. Physiol., June 1, 2006; 573(2): 395 - 412. [Abstract] [Full Text] [PDF]

				D. Enkvetchakul, I. Jeliazkova, and C. G. Nichols Direct Modulation of Kir Channel Gating by Membrane Phosphatidylinositol 4,5-Bisphosphate J. Biol. Chem., October 28, 2005; 280(43): 35785 - 35788. [Abstract] [Full Text] [PDF]

				C. A. Cukras, I. Jeliazkova, and C. G. Nichols Structural and Functional Determinants of Conserved Lipid Interaction Domains of Inward Rectifying Kir6.2 Channels J. Gen. Physiol., May 28, 2002; 119(6): 581 - 591. [Abstract] [Full Text] [PDF]

				D. W. Hilgemann, S. Feng, and C. Nasuhoglu The Complex and Intriguing Lives of PIP2 with Ion Channels and Transporters Sci. Signal., December 4, 2001; 2001(111): re19 - re19. [Abstract] [Full Text] [PDF]

				D.-K. Song and F. M. Ashcroft ATP Modulation of ATP-sensitive Potassium Channel ATP Sensitivity Varies with the Type of SUR Subunit J. Biol. Chem., March 2, 2001; 276(10): 7143 - 7149. [Abstract] [Full Text] [PDF]