Email: physiology@rosalindfranklin.edu Fax: 847.578.3265
Hawkins, Richard A Kim, Donghee
Najmabadi, Feridoon McCormack, Charles E. Peterson, Darryl R. Rasgado-Flores, Hèctor
Our laboratory uses the electrophysiology techniques of patch and whole-cell voltage clamping to investigate ion channels in non-excitable cells. Work has focused on channels in the proximal tubule and collecting duct of the kidney, with particular emphasis on the role of mechanosensitive (stretch-activated) ion channels. These channels alter their electrical gating properties as a function of membrane tension, acting as microtransducers that convert pressure and osmotic information into electrical currents. They may be important for both volume regulation and electrolyte homeostasis.
We are also studying the permeation properties of a cloned renal potassium channel (ROMK), expressed in Xenopus oocytes. This channel probably constitutes the principal route for renal K secretion in mammalian cortical collecting tubule and is essential for the bodys potassium balance. Site-directed mutagenesis is being used to explore structure-function relationships of this potassium channel. Chimeras have also been constructed by interchanging analogous regions of strong (IRK) and weak (ROMK) inward rectifiers. This has helped to define the structural basis for the different properties of these 2 important subfamilies of potassium channels.
The channel can be viewed from different angles by clicking and dragging your mouse across the image (works best with Safari web browser).
Kir1.1, homology-modeled on the bacterial K+ channel structure1P7B. The channel is composed of four identical protein chains, represented as backbone ribbons. Four potassium ions (red spheres) are located in the selectivity filter of the channel.
Homology modeling and Jmol scripting by Eric Walters, Dept. of Biochemistry and Molecular Biology.
Recent Publications
Sackin H, et al. (2007). External K Activation of Kir1.1 depends on the pH Gate. Biophysical Journal Vol 93: L14-L16.
Nanazashvili, M., Li,H., Palmer L.G., Walters D.E., and Sackin H. (2007). Moving the pH gate of the Kir1.1 inward rectifier channel. Channels Vol 1: 21 - 28
Zhang, Y., Sackin, H., and L.G. Palmer (2006). Localization of the pH gate in Kir1.1 channels. Biophysical Journal 91:2901-2909.
Sackin, H., Nanazashvili, M., Palmer, L.G., and Hui Li (2006). Role of conserved glycines in pH gating of Kir1.1 (ROMK). Biophysical Journal 90:3582-3589.
Sackin H, Nanazashvili, M., Palmer L.G., Krambis, M. and D.E. Walters. (2005). Structural locus of the pH gate in the Kir1.1 inward rectifier channel. Biophysical Journal. 88: 2597-2606.
Sackin H, L.G. Palmer, and M. Krambis. (2004). Potassium-dependent slow inactivation of Kir1.1 (ROMK) channels. Biophysical Journal. 86: 2145-2155. Dahlmann A, Li M, Gao ZH, McGarrigle D, Sackin H, and L. G. Palmer. (2004). Regulation of Kir channels by intracellular pH and extracellular K+: Mechanisms of Coupling J. Gen. Physiol. 123: 441- 454.
Sackin H, Vasilyev S., Palmer, L.G. and M. Krambis. (2003). Permeant cations and blockers modulate pH gating of ROMK channels. Biophysical Journal. 84: 910-921.
Sackin H, Syn S., Choe, H., Palmer, L.G. and E. Walters. (2001). Regulation of ROMK by extracellular cations. Biophysical Journal. 80: 683-697.
Choe, H., Sackin H, and Palmer, L.G. (2001). Gating Properties of Inward-Rectifier Potassium Channels: Effects of Permeant Ions. J. Memb Biol 184: 81-89.
Choe, H., Sackin H, and Palmer, L.G. (2000). Permeation Properties of Inward-Rectifier Potassium Channels and Their Molecular Determinants J. Gen. Physiol. 115: 391-404.
Choe, H., Palmer, L.G. and Sackin H. (1999). Structural determinants of gating in inward rectifier K channels. Biophysical Journal. 76: 1988-2003.
Frindt, G., Zhou, H., Sackin H. and Palmer, L.G. (1998). Dissociation of K channel density and ROMK mRNA in the rat cortical collecting tubule during K adaptation. Am. J. Physiol. 274(Renal) : F525-F531.
Choe, H., Sackin H, and Palmer, L.G. (1998). Permeation and Gating of an Inwardly Rectifying Potassium Channel: Evidence for a variable energy well.. J. Gen. Physiol. 112: 433 - 446.
Choe, H., Zhou, H., Palmer, L.G. and Sackin H.(1997). A conserved cytoplasmic region of ROMK modulates pH sensitivity, conductance, and gating. Am. J. Physiol. 273 (Renal) : F516-F529.