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Neuroscience Graduate Program at UCSF
Calcium Channel Modulation by Neurotransmitters and Drugs
Neurons in the brain possess at least several dozen different types of ion channels that control the movement of specific ions across the cell membrane. They are generally closed in resting neurons, but open transiently in response to changes in the membrane potential or in response to synaptically released neurotransmitters. The complex electrical signals generated by neurons involves the coordinated opening of many different types of channels during excitation. We are studying the cellular and molecular mechanisms by which neuronal ion channel activity can be modified by specific neurotransmitter and drug molecules. Experimental work uses biophysical techniques to understand the underlying kinetic mechanisms.
A major focus of our work is understanding the mechanism of modulation of voltage-gated calcium channels. Calcium channels play a central role in many neuronal processes including the release of neurotransmitters by exocytosis, axon outgrowth, gene expression, and neuronal survival. There are many different types of voltage-gated calcium channel in the brain that are derived from at least five gene families. Although calcium channels open within milliseconds following membrane depolarization, their expression and activity is highly regulated over a time span of minutes, hours, and days. One project has focused on the modulatory actions of glutamate, the main excitatory neurotransmitter in the brain. Calcium channel modulation by glutamate involves two distinct pathways: an inhibitory pathway that is selective for the N- and L-type channel and a pathway which leads to the selective facilitation of a novel class of L-type channel that is closely coupled to intracellular calcium stores. We are interested in understanding the cellular pathways responsible for these divergent regulatory pathways and the mechanisms that are responsible for the changes in channel activity. A variety of methods are being used to study coupling between intracellular calcium stores and membrane channels, including simultaneous recordings of calcium current and fluorescence measurements intracellular calcium levels in single cells and flash photolysis of intracellularly trapped caged compounds for rapid and precise changes in second messenger levels.
Link to Publications via PubMed
Chavis, P., Fagni, L., Bockaert, J., and Lansman, J.B. (1995) Modulation of calcium channels by metabotropic glutamate receptors in cerebellar granule cells. Neuropharm. 34(8):929-937.
Haws, C.M., Winegar, B., and Lansman, J.B. (1996) Block of L-type Ca2+ channels in skeletal muscle fibers by aminoglycoside antibiotics. J. Gen. Physiol. 107:421-432
Winegar, B., Haws, C.M. and Lansman, J.B. (1996) Subconductance block of mechanosensitive ion channels in skeletal muscle fibers by aminoglycoside antibiotics. J. Gen. Physiol. 107:433-443
Parri, H.R. and Lansman, J.B (1996) Multiple components of Ca2+ channel facilitation in cerebellar granule cells. Expression of facilitation during development in culture. J. Neurosci. 16:4890-4902.
Chavis, P., Fagni, L, Lansman, J.B, and Bockaert, J. (1996) Functional coupling between ryanodine receptors and L-type calcium channels in neurons. Nature 382:719-722 S
Jeff Lansman, Ph.D.
Phone
415-476-1322
Physical Address
513 Parnassus
S-1272
Mailing Address
UCSF, 513 Parnassus
Box 0450
San Francisco, CA
94143-0450
For Internal Campus Mail
Box 0444
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