Steven Kehl
Professor Emeritus
BCHCRF Scholar, UBC, 1988-1993
MRC Neuroendocrinology Unit, UK, 1984-1987
MRC Postdoctoral Fellow
PhD (Physiology) UBC, 1984
MSc (Biology) University of Waterloo, 1979
BSc (Biology) University of Waterloo, 1976
Email: steven.kehl@ubc.ca
Office: 604-822-2185
Research Interests
Potassium channels are protein-lined pores that span the lipid bilayer and act essentially as highly selective enzymes that catalyse the movement of potassium ions across the cell membrane. Potassium ion movement across the membrane tends to drive the membrane voltage toward the equilibrium potential for potassium (~ -90 mV), consequently these channels play a vital role in determining cell excitability and, by extension, cell function. For example, ATP-gated potassium channels play a role in coupling the increase of plasma glucose to insulin secretion; voltage-gated potassium channels affect the rhythm of the heart and influence chemical signalling between neurones in the brain.
From the many types of K channels that exist we have chosen to focus on voltage-gated K+ channels. In this class of channel the probability that the channel is open and conducting is determined by the membrane voltage. Using the voltage clamp technique we address questions such as the voltage-dependence of activation, the mechanism(s) of inactivation, the ionic selectivity of the channel pore and the influence of test substances on channel behaviour. Recently, the focus in the lab has shifted from potassioum channels expressed in pituitary cells (melanotrophs), to cloned channels. In this approach, and in collaboration with Dr. Fedida’s lab, molecular biological techniques are used to express normal and point-mutated K+ channels in a cell line (human embryonic kidney (HEK) cells) so that recording from a homogeneous population of channels is facilitated. Ultimately, by examining the effects of organic substances and ions (e.g. Zn2+, H+) on the behaviour of normal and mutant channels we hope to develop our understanding of structure/function relationships in these wonderfully interesting proteins.
Students who study in the lab may expect to learn voltage clamp recording of macroscopic and microscopic (single channel) currents using patch electrodes, the use of computers for data analysis and modelling of current behaviour and, finally, the application of molecular biology in the expression of wild-type and mutated potassium channels.
- Cheng YM, Fedida D, Kehl SJ*. (2013) ShakerIR and Kv1.5 mutant channels with enhanced slow inactivation also exhibit K⁺o-dependent resting inactivation. Pflugers Archiv 465(11): 1545-1555. [IF 3.07].
- Kehl SJ, Fedida D, Wang Z. (2013) External Ba2+ block of Kv4.2 channels is enhanced in the closed-inactivated state. American Journal of Physiology (Cell Physiology) 304 (4):370 – 381. [IF 3.67].
- Cheng YM, Fedida D, Kehl SJ*. (2010) Kinetic analysis of the effects of H+ or Ni2+ on Kv1.5 current shows that both ions enhance slow inactivation and induce resting inactivation. Journal of Physiology 588:3011 – 3030. [IF 4.54].
- Wang Z, Wong NC, Cheng Y, Kehl SJ, Fedida D. (2009) Control of voltage-gated K+ channel permeability to NMDG+ by a residue at the outer pore. Journal of General Physiology 133:361-374. [IF 4.57].