My Contact Information

Emeritus Professor of Biochemistry and Biophysics
Ph.D. University of Pennsylvania 1968

Neurotransmitter molecules released from presynaptic neuronal stores act on post-synaptic neuronal receptors. Action of most transmitters is terminated when they are sequestered in glial and neuronal cells near the synapse following transmitter uptake by Na+-coupled transport systems. Efficient function of the relevant transport systems is imperative for keeping extracellular concentrations of transmitters low (~ 1 uM) so that the nervous system remains poised for further transmission of excitatory and inhibitory signals. Compromised function of neurotransmitter transport systems often occurs concomitantly with various neurodegenerative diseases, although it can be difficult to discern whether compromised function is a cause or a result of the pathophysiological condition. Some aspects of CNS pathophysiology are known to occur because glutamate, the most abundant excitatory transmitter, becomes a potent neurotoxin if it remains in the synapse for even short intervals following its release from the presynaptic neuron.

Our current projects focus on characterizing the function and regulation of Na+-coupled glutamate transporters in astrocytic glial cells. Presynaptic neurons do not have capability for resynthesis of glutamate from glycolytic intermediates, so carbon equivalent to that captured by astrocytes as glutamate must be returned to the neuron by some alternative route, and in some form that avoids activation of neuronal glutamate receptors during the return trip. The return of carbon from astrocytes must also occur at rates sufficient to sustain neuronal synthesis and repackaging of glutamate for subsequent reuse as a transmitter. Although it is recognized that net transfer of metabolites must occur across the glial cell membrane in both directions to accommodate CNS function, details regarding the precise pathway followed during the neuronal/glial/neuronal carbon cycle are not well understood.

Work is also in progress aimed at defining the role that protein kinase C (PKC) plays in regulating function of various CNS transport systems involved in the carbon shuttle. Activation of PKC causes a pronounced increase in glutamate transport capability by cultured astrocytes. We are exploring the mechanism by which PKC modulates astrocytic glutamate transport and metabolism.

Recent Publications

Kimmich GA, Roussie JA, Randles J (2002) Aspartate aminotransferase isotope exchange reactions: implications for glutamate/glutamine shuttle hypothesis. Am J Physiol Cell Physiol, 282:C1404-13

Kimmich GA, Roussie J, Manglapus M, Randles J (2001) Characterization of Na+-coupled glutamate/aspartate transport by a rat brain astrocyte line expressing GLAST and EAAC1. J Membr Biol, 182:17-30

Kimmich GA, Laties VG, Marquis RE (2000) Graduate Education in Biomedical Science: Partners in Inquiry. In: 75 Years of Achievement - The University of Rochester Medical Center - Teaching, Discovery, Caring, J. Cohen and R. Joynt, eds., University of Rochester Press, pp. 77-95

Wilson JJ, Randles J, Kimmich GA (1998) Na+-coupled alanine transport in LLC-PK1 cells: the relationship between the Km for Na+ at low [Alanine] and potential dependence for the system. J Membr Biol, 165:275-82

Wilson JJ, Randles J, Kimmich GA (1996) A model for the kinetic mechanism of sodium-coupled L-alanine transport in LLC-PK1 cells. Am J Physiol, 270:C49-56

Bennett E, Kimmich GA (1996) The molecular mechanism and potential dependence of the Na+/glucose cotransporter. Biophys J, 70:1676-88

Kimmich GA, Randles J, Wilson J (1994) Na(+)-coupled alanine transport in LLC-PK1 cells. Am J Physiol, 267:C1119-29

Contact Information

E-Mail: gkimmich@rochester.rr.com

George A. Kimmich
Department of Biochemistry and Biophysics
University of Rochester School of Medicine and Dentistry
601 Elmwood Ave, Box 712
Rochester, New York 14642

Office: Medical Center 3-6820
Telephone: (585) 275-3704; Lab: (585) 275-1729 Fax: (585) 275-6007