The Lee lab's research centers on voltage-gated (Cav) Ca2+ channels and their roles in the nervous and cardiovascular systems. We view Cav channels as macromolecular complexes, the components of which regulate their properties and involvement in cellular transduction cascades. One focus is on Cav1 L-type channels at sensory ¡§ribbon¡¨ synapses in the retina and inner ear, where Cav protein interactions transform presynaptic Ca2+ signals required for high-throughput neurotransmitter release.
A second focus is on protein interactions regulate Cav1 channels involved in spontaneous firing (pacemaking) in the heart and brain. Our approach is multidisciplinary: we use patch-clamp electrophysiology for studies of Cav channel modulation and exocytosis; molecular biology, protein chemistry, and immuncytochemistry for analysis of Cav protein interactions; and gene silencing methods (siRNA, targeted gene disruption) and in vivo electrophysiology to evaluate the physiological consequences of Cav protein interactions in the context of hearing, vision, and cardiac rhythmicity. Our long-term goal is to develop pharmacological strategies to target cell-type and tissue-specific Cav regulatory mechanisms, which may prove more selective than current Cav agonists and antagonists in the treatment of neurological and cardiovascular disease.
Selected Publications:
Milner, T.A., Rosin, D.L., Lee, A., and S.A. Aicher (1999) ?Ñ2A-adrenergic receptors are primarily presynaptic heteroreceptors in the C1 area of the rat rostral ventrolateral medulla. Brain Res. 821:200-11.
Milner, T.A. Lee, A., Aicher, S.A., and D.L. Rosin (1998) Hippocampal ?Ñ2A-adrenergic receptors are located predominantly presynaptically but are also found postsynaptically and in selective astrocytes. J. Comp. Neurol. 395:310-27
Lee, A., Rosin, D.L., and E.J. Van Bockstaele (1998) ?Ñ2A-adrenergic receptors in the rat nucleus locus coeruleus: subcellular localization in catecholaminergic dendrites, astrocytes, and presynaptic axon terminals. Brain Res. 795:157-69
Lee, A., Rosin, D.L., and E.J. Van Bockstaele (1998) Ultrastructural evidence for prominent postsynaptic localization of ?Ñ2C-adrenergic receptors in catecholaminergic dendrites in the rat nucleus locus coeruleus. J. Comp. Neurol. 394:218-29
Lee, A., Wissekerke, A.E.W., Rosin, D.L., and K.R. Lynch (1997) Localization of ?Ñ2C-adrenergic receptor immunoreactivity in central catecholaminergic neurons. Neuroscience 84:1085-96
Rosin, D.L., Talley, E., Lee, A., Stornetta, R.L., Gaylinn, B., Guyenet, P.G., and K.R. Lynch (1996) Distribution of ?Ñ2C-adrenergic receptor-like immunoreactivity in the rat central nervous system. J. Comp. Neurol. 372: 135-165
Talley, E., Rosin, D.L., Lee, A., Guyenet, P.G., and K.R. Lynch (1996) Distribution of ?Ñ2A-adrenergic receptor-like immunoreactivity in the rat central nervous system. J. Comp. Neurol. 372:111-134
Lee, A., Talley, E., Rosin, D.L., and K.R. Lynch (1995) Characterization of ?Ñ2A-adrenergic receptors in GT1 neurosecretory cells. Neuroendocrinology 62:215-225
Baraban, S.C., Lothman, E.W., Lee, A., and P.G. Guyenet (1995) Kappa opioid receptor-mediated suppression of voltage-activated K+ current in a catecholaminergic cell line. J. Pharmacol. Exp. Ther. 273:927-933
Lee, Y.S., Lee, H.J., Crain, R.C., Lee, A., and S.J. Korn (1994) Polyunsaturated fatty acids modulate stomatal aperture and two distinct K+ channels in guard cells. Cellular signalling 6:181-186
