Although it generally is appreciated that Ca channels play crucial roles in the shaping of action potentials and firing patterns, as well as in the control of transmitter release at nerve terminals, the study of these roles has been limited by the availability of selective tools for blocking Ca channels. The recent isolation of omega-Aga-IVA (from spider venom) constitutes a significant advance since this toxin may be used to target a unique population of Ca channels whose roles were difficult to isolate previously. Funds are requested to continue these studies in three different ways: 1) patch-clamp recordings from tissue slices or freshly isolated neurons to investigate whether the toxin blocks more than one population of Ca channels (as suggested recently by R. W. Tsien and collaborators); 2) photometric studies of presynaptic Ca transients to determine the regulation of synaptic strength by transmitters that affect presynaptic Ca channels differentially; and 3) patch-clamp recordings of Purkinje cells in combination with photometric measurements of Ca to study the link between P-type Ca channels and internal Ca release, and their contribution to the processing of synaptic inputs. Since Ca channels sensitive to omega-Aga-IVA are ubiquitous in the CNS, there is no question that these studies will provide greater insight into the many cellular functions controlled by calcium (e.g. promotion of neuronal growth, regulation of genes and enzymes, etc.) as well as into the pathological situations that arise when Ca homeostatic mechanisms are disrupted, as is thought to occur with epilepsy, excitotoxicity, and neuronal death.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
3R29NS034550-04S1
Application #
6092055
Study Section
Physiology Study Section (PHY)
Program Officer
Liu, Yuan
Project Start
1995-09-01
Project End
2000-07-31
Budget Start
1998-08-01
Budget End
1999-07-31
Support Year
4
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Boston University
Department
Pharmacology
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118