Ph.D, Australian National University
Fax: (631) 632-6661
Basic Sciences Tower 6
David McKinnon received a B.Sc. in Physiology from the University of New South Wales, Australia, in 1983 and a Ph.D. in Physiology from the John Curtin School of Medical Research, Australian National University in 1987. Between 1987 and 1990, he was a Post-Doctoral Fellow at the Salk Institute and then at Washington University. In 1991 he joined the State University of New York at Stony Brook as Assistant Professor of Neurobiology and Behavior and was promoted to full professor in 2005.
Homeostatic Regulation of Ion Channel Expression
Remarkably little is known about the evolution of complex physiological systems, as opposed to the evolution of individual physiologically important proteins. Regualtions of ion channel expression is critical for the maintenance for the function of electrically excitable cells. Surprisingly, human genetic studies have shown that there is little feedbackregulating channel expression fromt hej remaining allele or from other genes that could compensate for loss. In principle, there are a large number of points at which homeostatic regualtioncould act to control ion channel expression, but in practice, very few homeostatic regulatory mechanisms appear to function in the adult. Understanding what homeostatic mechanisms are and are not, available to regulate the function of these systmes is the3 focus of our study. We use conditional knockout mice in which we selectly eliminate, one or both alleles of a given ion channel gene in the adult mouse in order to study the consequences of that loss on the molecular and cellular physiology of the animal.
Currently we are interested in two questions:
- How does long-term stress modify nervous system and cardiovascular system function?
- What are the effects of chemotherapeutic agents on cognitive function and how are these effects mediated?
See our laboratory web page for more details on these projects and work in the laboratory.
- Laboratory Personnel
- McKinnon D. and Rosati, B. (2016) Transmural gradients in ion channel and auxiliary subunit expression. Prog. Biophys. Mol. Biol., S0079-6107
- Kim M, MacCarthy T, Rosati B, McKinnon D. (2015), Regulatory evolution and voltage-gated ion channel expression in squid axon: selection-mutation balance and fitness cliffs, PLoS One. 2015 Apr 13;10(4):e0120785
- Wang HZ, Rosati B, Gordon C, Valiunas V, McKinnon D, Cohen IS, Brink PR (2015), Inhibition of histone deacetylase (HDAC) by 4-phenylbutyrate results in increased junctional conductance between rat corpora smooth muscle cells, Front Pharmacol. 2015 Feb 3;6:9
- Yan Q., Masson R., Ren Y., Rosati B., McKinnon D. (2012) Evolution of CpG island promoter function underlies changes in KChIP2 potassium channel subunit gene expression in mammalian heart. Proc. Natl. Acad. Sci., 109, 1601-1606.
- Rosati, B., Yan, Q., Lee, M.S, Liou, S-R., Ingalls, B., Foell, J., Kamp, T.J. and McKinnon, D. (2011) Robust L-Type Calcium Current Expression following Heterozygous Knockout of the Cav1.2 Gene in Adult Mouse Heart. J. Physiol., 589, 3275–3288. [link]
- Rosati, B. and McKinnon, D. (2009) Structural and regulatory evolution of cellular electrophysiological systems. Evol Dev, 11, 610-618. [pdf]
- Rosati, B., Dong, M., Cheng, L., Liou, S.-R., Yan, Q., Park, J.Y., Shiang, E., Sanguinetti, M., Wang, H.-S. and McKinnon, D. (2008) Evolution of ventricular myocyte electrophysiology. Physiol Genomics, 35, 262-272. [pdf]
- Rosati, B. and McKinnon, D. (2004) Control of Ion Channel Expression. Circ. Res., 94, 874-883.
- Rosati, B., Grau, F., Rodriguez, S., Li, H., Nerbonne J. M. and McKinnon, D. (2003) Concordant Expression of KChIP2 mRNA, Protein and Transient Outward Current throughout the Canine Ventricle. J. Physiol., 548, 815-822.
- Wang, H.-S., Pan, Z., Shi, W., Brown, B. S., Wymore, R.S., Cohen, I. S., Dixon, J. E. and McKinnon, D. (1998) KCNQ2 and KCNQ3Potassium Channel Subunits: Molecular Correlates of the M-Channel. Science, 282, 1890-1893.
- Dixon, J. E., Shi, W., Wang, H.-S., MacDonald, C., Yu, H., Wymore, R. S., Cohen, I. S. and McKinnon, D. (1996). Role of the Kv4.3 K+ channel in ventricular muscle: a molecular correlate for the transient outward current. Circ. Res., 79, 659-668.
- Wang, H.-S. and McKinnon, D. (1995). Potassium currents in prevertebral and paravertebral sympathetic neurones: Control of firing properties. J. Physiol., 485, 319-335.
- McKinnon, D. (1989) Isolation of a cDNA clone coding for a putative second potassium channel indicates the existence of a gene family. J. Biol. Chem., 264, 8230-8236.
- McKinnon, D. and Ceredig, R. (1986) Changes in the expression of potassium channels during mouse T cell development. J. Exp. Med., 164, 1846-1861.
- Barbara Rosati - Research Assistant Professor
- Shian-Ren Liou – Postdoctoral Associate