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.
BSc (Biology) University of Waterloo, 1976
MSc (Biology) University of Waterloo, 1979
PhD (Physiology) UBC, 1984
MRC Postdoctoral Fellow
MRC Neuroendocrinology Unit, UK, 1984-1987
BCHCRF Scholar, UBC, 1988-1993
- Kwan DCH, Fedida D & Kehl, SJ, Single channel analysis of the inhibition of hKv1.5 current by external protons. Biophys. J. In press.
- Zhang S, Eduljee C, Kwan DCH, Kehl SJ & Fedida D. Constitutive inactivation of the Kv1.5 mutant channel, H464G, in K+-free solutions at physiological pH. Cell Biochem. Biophys. 34(2):221-230, 2005.
- Fedida D, Zhang S, Kwan DCH, Eduljee C & Kehl SJ. Synergistic inhibition of the maximum conductance of Kv1.5 channels by extracellular K+ reduction and acidification. Cell Biochem. Biophys. 43(2):231-242, 2005.
- Kwan DCH, Eduljee C, Lee LL, Zhang S, Fedida D & Kehl SJ. The external K+ concentration and mutations in the outer pore mouth affect the inhibition of Kv1.5 current by Ni2+. Biophys. J. 86 (4):2238-2250, 2004.
- Zhang, S., Kehl, S.J., Fedida, D. Modulation of Kv1.5 potassium channel gating by extracellular zinc. Biophysical Journal, 81:125-136, 2001.
- Zhang, S., Kwan, D.H.C., Fedida, D., Kehl, S.J. External K+ relieves the block but not the gating shift caused by Zn2+ in human Kv1.5 channels. J. Physiol. 532.2:349-358, 2001.
- Kehl, S.J. Eicosatetranoic acid (ETYA), a non-metabolizable analogue of arachidonic acid, blocks the fact-inactivating potassium current of rat pituitary melanotrophs. Can. J. Physiol. Pharmacol., 79:1-8, 2001.
- Kehl, S.J. & Wong, K. Large conductance calcium-activated potassium channels of cultured rat melanotrophs. J. Membrane Biology, 150:219-230, 1996.
- Davidson, J.-L. & Kehl, S.J. Changes of activation and inactivation gating of the transient potassium current of rat pituitary melanotrophs caused by micromolar Cd2+ and Zn2+. Can. J. Physiol. Pharmacol. 73:36-42, 1995.
- Kehl, S.J. 4-aminopyridine causes a voltage-dependent block of the transient outward current in acutely dissociated adult rat melanotrophs. J. Physiol. 431:512-528, 1990.