People / Dunlap Laboratory

Kathleen Dunlap, Ph.D.
Professor of Neuroscience
Office Phone: (617) 636-4942
Lab Phone: (617) 636-4938
Fax: (617) 636-0576
kathleen.dunlap@tufts.edu

Search for recent publications by Kathleen Dunlap

Research Interests

Our laboratory is interested the roles of calcium channels in neuronal function. In particular, our work is focused both on calcium channels in nerve terminals that are responsible for transmitter release and on calcium channels in cell bodies that are responsible for regulating membrane excitability and gene transcription. Our studies in nerve terminals involve the tottering mouse, which carries a point mutation in the gene encoding P-type calcium channels; these animals exhibit frequent epileptic seizures and a dramatic gait disorder. Our results suggest that the mutation leads to an alteration in the balance of excitation/inhibition in the cerebellum, providing a possible explanation for the motor deficits in this animal. Given that human mutations in the homologous gene also result in similar gait disorders, we anticipate that our results will likely impact on the understanding of human motor disease.

Our work on somatic calcium channels has focused on the molecular mechanisms by which the channels are modulated by receptor-G protein-coupled pathways. We have identified three biochemically and biophysically distinct mechanisms that bring about channel inhibition. We are now exploring the physiological implications of such modulation on calcium-dependent responses in cell bodies. Specifically, we would like to determine the consequences of modulating calcium influx on membrane excitability (via calcium-activated chloride channels) and gene transcription (via calcium-activated transcription factors).

Lab Members

Marian Haburcak, Postdoctoral Fellow
Chuang Du, Electrophysiology Core Manager

Selected Publications

Erickson, M., Haburcak, M., Smuckler, L., and Dunlap, K. (2007) Altered functional expression of Purkinje Cell calcium channels precedes motor dysfunction in tottering mice. Neuroscience (in press)

Dunlap, K. (2007) Calcium channels are models of self-control. J. Gen. Physiol. 129:379-383

Olsen, D., Dunlap, K., and Jacob, M. (2007) Kainate receptors and RNA editing in cholinergic neurons. J Neurochemistry 101:327-342

Ikeda, S.R. and Dunlap, K. (2007) Calcium channels diversify their signaling portfolio. Nature Neuroscience 10:269-271

Mukherjee, R.S., McBride, E.W., Beinborn, M., Dunlap, K., and Kopin, A.S. (2006) Point mutations in either subunit of the GABA_B receptor confer constitutive activity to the heterodimer. Molec. Pharm. 70:1406-1413

Tosetti, P. and Dunlap, K. (2004) Assays of RGS3 activation and modulation. Methods Enzymol. 390:99-119

Tosetti, P., Pathak, N., Jacob, M.H., and Dunlap, K. (2003) Calcium directly activates RGS3 proteins in sensory neurons. PNAS 100:7337-7342

Tosetti, P., Parente, V., Taglietti, V., Dunlap, K., and Toselli, M. (2003) Chick RGS2L demonstrates concentration-dependent selectivity for G_q/11 and G_i/o pathways that inhibit L-type Ca²⁺ channels. J. Physiol. 549:157-169

Zhou, Y.D., Turner, T.J., and Dunlap, K (2003) Enhanced G protein-dependent modulation of excitatory synaptic transmission in cerebellum of the Ca²⁺ channel mutant mouse, tottering. J. Physiol. 547:497-507

Tosetti, P., Turner, T.J., Lü, Q., and Dunlap, K. (2002) Unique isoform of G_a-interacting protein (RGS-GAIP) selectively discriminates between two G_o-mediated pathways that inhibit Ca²⁺ channels. J. Biol. Chem. 277:46001-46009