Structure & function of inward rectifier K channels
Dr. Sackin is a graduate of Brown University (1970, Physics) and received his Ph.D. from Yale University (1978, Biophysics) where he remained as Postdoctoral fellow (1978-1981) before joining the faculty at Cornell Univ. Medical College as Assistant, and then Associate Professor (1981-1997). Dr. Sackin joined the faculty of The Chicago Medical School (Rosalind Franklin University), where he has been full Professor since 1998. Dr. Sackin's research has been continuously funded by NIH (NIDDK) and Am. Heart (1981-2013).
Our laboratory utilizes 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 permeation and gating of inward rectifier K channels (Kir) using both heterologous expression of channels in Xenopus oocytes and direct incorporation of channel protein into liposomes. This channel constitutes a principal pathway for renal K secretion in mammalian cortical collecting tubule and is essential for the body's potassium balance.
Site-directed mutagenesis of Kir channels in our lab has helped to define the structural basis for a primary ligand gate at the bundle-crossing of inner transmembrane helices as well as a secondary K-dependent gate at the selectivity filter, operating in series with the bundle-crossing gate.
The picture shows 2 of 4 subunits of the closed-state of the Kir1.1b inward rectifier potassium channel, found in the thick ascending limb, connecting tubule, and cortical collecting duct of the mammalian kidney. The channel protein spans the membrane where the external solution is at the top, and the cytoplasm is at the bottom. It is regulated by cytoplasmic ATP, internal phosphorylation and cytoplasmic pH. The primary gate of the channel is a pH gate, formed by occlusion of the permeation path at the bundle-crossing of inner transmembrane helices. However, another gate also exists at the selectivity filter. This gate is in series with the bundle-crossing gate and behaves like the C-type inactivation gate of voltage gated Kv channels, found throughout the nervous system.
A list of relevant publications is listed under Important Links / Publications