Adenosine Triphosphate (ATP) is present in many types of synaptic vesicles, but at most synapses it has not known function. The recent discovery that chick skeletal muscles fibers are excited by ATP (Kolb and Wakelam, 1983; Hume and Honig, 1986) provides an excellent opportunity for examining the role of ATP at synapses, since the neuromuscular junction is by far the best characterized synapse, both in maturity and during development. Muscle cells characterized synapse, both in maturity and during development. Muscle cells in culture are very accessible for electrophysiological and biochemical studies, so these observations also open the way for detailed studies of the cellular and molecular basis of ATP mediated excitation.
The specific aims of this project are: 1. To resolve conflicting results regarding the nature of the single channels that underlie the ATP evoked depolarization. 2. To determine whether a second messenger system is involved in the ATP evoked depolarization. 3. To examine the time course and mechanism of the long term desensitization that this response displays. 4. To test the hypothesis that receptor activation involves an extracellular phosphorylation. 5. To determine any functional role that ATP receptors play in neuromuscular transmission or in muscle development. These experiments are designed to further understanding of the function of a receptor found on muscle precursor cells and young muscle cells. The early appearance of this receptor suggests that it may play a role in the development of muscle cells or in the formation of neuromuscular junctions. Knowledge of the cellular interactions that control normal development would provide a basis for understanding, and perhaps ameliorating, medically relevant deficits in nerve and muscle function.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS025782-03
Application #
3411230
Study Section
Physiology Study Section (PHY)
Project Start
1988-02-01
Project End
1991-01-31
Budget Start
1990-02-01
Budget End
1991-01-31
Support Year
3
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
Schools of Arts and Sciences
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Zhou, Z; Hume, R I (1998) Two mechanisms for inward rectification of current flow through the purinoceptor P2X2 class of ATP-gated channels. J Physiol 507 ( Pt 2):353-64
Lin, X; Hume, R I; Nuttall, A L (1995) Dihydropyridines and verapamil inhibit voltage-dependent K+ current in isolated outer hair cells of the guinea pig. Hear Res 88:36-46
Thomas, S A; Hume, R I (1993) Single potassium channel currents activated by extracellular ATP in developing chick skeletal muscle: a role for second messengers. J Neurophysiol 69:1556-66
Lin, X; Hume, R I; Nuttall, A L (1993) Voltage-dependent block by neomycin of the ATP-induced whole cell current of guinea-pig outer hair cells. J Neurophysiol 70:1593-605
Dingledine, R; Hume, R I; Heinemann, S F (1992) Structural determinants of barium permeation and rectification in non-NMDA glutamate receptor channels. J Neurosci 12:4080-7
Hume, R I; Dingledine, R; Heinemann, S F (1991) Identification of a site in glutamate receptor subunits that controls calcium permeability. Science 253:1028-31
Thomas, S A; Zawisa, M J; Lin, X et al. (1991) A receptor that is highly specific for extracellular ATP in developing chick skeletal muscle in vitro. Br J Pharmacol 103:1963-9
Thomas, S A; Hume, R I (1990) Irreversible desensitization of ATP responses in developing chick skeletal muscle. J Physiol 430:373-88
Thomas, S A; Hume, R I (1990) Permeation of both cations and anions through a single class of ATP-activated ion channels in developing chick skeletal muscle. J Gen Physiol 95:569-90
Hume, R I; Thomas, S A (1989) A calcium- and voltage-dependent chloride current in developing chick skeletal muscle. J Physiol 417:241-61

Showing the most recent 10 out of 11 publications