Hypertension, diabetes, and obesity; endocrine
pharmacology and metabolism; excitability in cells of the pancreas
hypothalamic neurons and the vasculature; microscopic spectroscopy
and imaging.
Cell Energetics and Excitability
The relations between cell metabolism and excitation-secretion coupling in
the beta cell of the pancreas and hypothalamic neurons, and excitation-contraction
coupling in vascular smooth muscle are primary research interests.
The overall goal is to elucidate the mechanisms which lead to
the development of diabetes and its complications. Microscopic
spectroscopy and imaging techniques are used to study these issues
in single living cells.
For the beta cell and hypothalamic neuron models, experiments
are designed to elucidate the processes which link glucose metabolism
to changes in plasma membrane potential, and therefore, secretion
(i.e. insulin or neurotransmitter). The second area of research
is centered on understanding the mechanisms by which metabolism
is integrated with energy transducing processes in cardiac and
vascular smooth muscle cells. This relates to issues of
excitation-contraction coupling, oxygen sensitivity and the regulation
of intracellular Ca2+ in normal and the hypertensive
state.
In order to study these questions, micro-optical spectroscopy
and imaging techniques are used to study the subcellular distribution
of ions and molecules involved in these processes in single living
cells. In addition, monoclonal antibodies are used to monitor
and/or modulate the subcellular distribution of specific molecules.
Current work in both projects involves analysis of molecular distributions
(eg. protein kinase C, hexokinase) during transition from rest
to cell activation (secretion or contraction) in single cells
maintained on the stage of a microscope. Distributions of
fluorescent enzymes, metabolite levels, cell Ca2+ and
cell length (contractility) are monitored using a digital imaging
microscopy.
Ford, B.K., S.M. Murphy, C.E. Volin, R.M. Lynch, and M.R. Decour:
Computed-Tomography based video-rate spectral imaging for fluorescence
microscopy; Biophys. J. 80:(Feb), 2001.
Lynch, R.M., L.S. Tompkins, H.L. Brooks, A.A. Dunn-Meynell and
B.E. Levin: Localization of glucokinase gene expression
in the rat brain. Diabetes 49(5):693-700, 2000.
Tang, Q., R.M. Lynch, F.Porreca and J. Lai: Dynorphin A
mediates an increase in intracellular calcium in cultured neurons
via a non-opiod, non-NMDA mechanism. J Neurophysiol. 83(5):2610-2616,
2000.
Lynch, R.M., K. D. Nullmeyer, B.K. Ford, L.S. Tompkins, V.L.
Sutherland and M.R. Descour: Multi-parametric analysis of
cellular and subcellular function by spectral imaging. S.P.I.E.
Proceedings 3924:216-228, 2000.
Richmond, K.N, R.D. Shonat, R.M. Lynch and P.C. Johnson:
The Critical Oxygen Tension of Skeletal Muscle In Vivo. Am. J.
Physiol: Heart Circ. 277:H1831-H1840, 1999.
Martinez-Zaguilan, R., L.S. Tompkins, R.J. Gillies and R.M. Lynch:
Simultaneous Measurements of Calcium and pH in Cell Populations.
In: Calcium Signaling Protocols, Meth. Molec. Biol. Series, Vol.
114: (Ch. 20): pp. 287-306, editor, D.G. Lambert, Humana
Press, 1999.
