DAVID KRIZAJ
David Krizaj
email: David.Krizaj@hsc.utah.edu		 Associate Professor of Ophthalmology & Visual Science

The Krizaj Lab
Cellular Neuroscience
Neurobiology of Disease

B.S. 1986, University of Ljubljana, Slovenia; M.S. 1993, New York University; Ph.D. 1994, New York University.

RESEARCH:

Calcium regulation and synaptic communication in the vertebrate retina

David Krizaj's laboratory is interested in the relationship between intracellular signaling pathways and neurotransmission in the retina with the main focus on the photoreceptor synapse. Rod and cone output synapses are different from most neuronal synapses in that unstimulated cells continually release synaptic vesicles whereas the sensory stimulus (light) suppresses transmitter release in a graded intensity-dependent manner. The lab is interested in how non-conventional signaling pathways such as intracellular calcium stores, calcium transporters and store-operated calcium channels collaborate with voltage-operated signals to modulate this graded exocytosis. For example, recent experiments elucidated the roles of ryanodine receptors, mitochondria and TRPC channels in both spatiotemporal calcium signaling in photoreceptors, and neurotransmission. Another project studies the role of TRP channels in glaucoma, a nasty blinding disease. A third project is focused on the role of glutamate-glutamine cycling at the photoreceptor synapse.

Light responses from photoreceptors and postsynaptic bipolar/horizontal neurons are recorded electrophysiologically with ERGs, perforated or whole cell patch methods whereas calcium signals are measured simultaneously with high-resolution EMCCD cameras or an inlab Zeiss LSM 510-based confocal imaging system. The role of specific signaling pathways is studied as their constituent elements are eliminated with transfected/electroporated RNAi or by using knockout animals. A TIRF system will be set up in 2008 to study trafficking of GFP-tagged channels in photoreceptor membranes.

Selected Publications

Szikra, T., and Krizaj, D. (2009) Calcium signals in inner segments of photoreceptors. In: The Visual Transduction Cascade: Basic and Clinical Principles; Eds J. Tombran-Tink and C. Barnstable, Humana Press, Totowa, NJ.

Szikra, T., Cusato, K., Thoreson, W.H., Bartoletti, M. and Krizaj, D. (2008) Store-operated calcium channels regulate visual function. Journal of Physiology, 586:4859-4875.

Witkovsky, P., Gabriel, R., and Krizaj, D. (2008) Anatomical and neurochemical characterization of dopaminergic interplexiform processes in mouse retina. Journal of Comparative Neurology, 510:158-174.

Szikra, T., and Krizaj, D. (2007) Intracellular organelles and calcium homeostasis in rods and cones. Visual Neuroscience, 24:733-743.

Duncan, J., Yang, H., Doan, T., Silverstein, B., Murphy, G., Nune, G., Liu, X., Copenhagen, D.R., Rieke, F., Tempel, B.L., and Krizaj, D. (2006) Scotopic visual signaling in the mouse retina is modulated by high affinity plasma membrane calcium extrusion. Journal of Neuroscience, 26:7201-7211.

Szikra, T. and Krizaj, D. (2006) The dynamic range and domain-specific signals of intracellular calcium in photoreceptors. Neuroscience, 141:143-155.

Krizaj, D. (2005) Compartmentalization of calcium entry pathways in mouse rods. European Journal of Neuroscience, 22:3292-3296.

Krizaj, D., Lai, T., and Copenhagen, D.R. (2003) Ryanodine stores and calcium regulation in inner segments of salamander rods and cones. Journal of Physiology, 547:761-774.

Krizaj, D., Bao, J.X., Schmitz, Y., Witkovsky, P., and Copenhagen, D.R. (1999) The action of caffeine on glutamate release at the rod photoreceptor synapse. Journal of Neuroscience, 19:7249-7261.

Krizaj, D., and Copenhagen, D.R. (1998) Compartmentalization of calcium extrusion mechanisms in the outer and inner segments of photoreceptors. Neuron, 21:249-256.

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