Ph.D., University College, London
Professor
Department of Neuroscience
456 Sidney Frank Hall of Life Sciences
Tel: (401) 863-1092
Email: Diane_Lipscombe@Brown.edu
Go to lab web page

Our research program is centered on the study of voltage-gated calcium channels in neurons. Voltage-gated calcium channels regulate the rapid entry of calcium ions into neurons during membrane depolarization. Several congenital, neurological disorders including ataxia, epilepsy and migraine, link to calcium channel genes underscoring their critical role in supporting neuronal function. Neurons can select from a multitude of calcium channel genes, regulate the pattern of alternative messenger RNA splicing of each gene, and determine the subunit composition of the final calcium channel complex. The resulting structural diversity among members of the voltage-gated calcium channel family underlies their ability to couple to a vast array of calcium signaling pathways in neurons, including regulation of gene transcription, neurotransmitter release, neurite outgrowth, and rhythmic firing. Our laboratory has been particularly interested in alternative splicing as a mechanism to fine tune calcium channel activity in different parts of the nervous system. We employ a variety of techniques in our research including, molecular cloning, site directed mutagenesis, heterologous expression of cloned channels, and electrophysiological analysis. The citations below offer insight into where we have been, our web page shows where we are now and gives a flavor of where we hope to go.

Fairbrother, W & Lipscombe, D (2008). Repressing the neuron within. Bioessays 30:1-4

Raingo, J, Castiglioni, AJ & Lipscombe, D (2007). Alternative splicing controls G protein-dependent inhibition of N-type calcium channels in nociceptors. In press. Nature Neuroscience

Altier C, Dale CS, Kisilevsky AE, Chapman K, Castiglioni AJ, Matthews EA, Evans RM, Dickenson AH, Lipscombe D, Vergnolle N, Zamponi GW. (2007) Differential role of N-type calcium channel splice isoforms in pain. J Neurosci, 27, 6363-73.

Gray AC, Raingo J, Lipscombe D. (2007) Neuronal calcium channels: Splicing for optimal performance. Cell Calcium. 42:4-5.

Lipscombe, D & Raingo, J (2007). Alternative Splicing Matters: N-type Calcium Channels in Nociceptors. Channels 1:225-227.

Castiglioni, AJ, Raingo, J & Lipscombe, D. (2006) Alternative splicing in the C-terminus of CaV2.2 controls surface expression and gating of N-type calcium channels. Journal of Physiology. 576:119-134.

Wyllie, DJA, Johnston, AR, Lipscombe, D & Chen, PE. (2006) Single-channel analysis of a point mutation of a conserved serine residue in the S2 ligand binding domain of the NR2A NMDA receptor subunit. Journal of Physiology 574:477-489.

Lipscombe, D & Raingo, J (2006). Internalizing channels: a mechanism to control pain? Nature Neuroscience 9:8-10.

Lipscombe, D (2005). Neuronal proteins custom designed by alternative splicing. Current Opinions in Neuroscience 15:358-363.

Helton, TD, Xu, W, & Lipscombe, D (2005). Neuronal L-type calcium channels open quickly and are blocked slowly. J. Neuroscience 25: 10247-10251.

Lipscombe, D. (2005) Ion channels. The Encyclopedia of Life Sciences. Macmillan Press.

Bell, T. J., C. Thaler, et al. (2004). "Cell-specific alternative splicing increases calcium channel current density in the pain pathway." Neuron41(1): 127-38.

Lin, Y., S. I. McDonough, et al. (2004). "Alternative Splicing in the Voltage-Sensing Region of N-Type CaV2.2 Channels Modulates Channel Kinetics." J Neurophysiol92(5): 2820-30.

Lipscombe, D., Xu, W. & Helton, TD. (2004) Neuronal L-type calcium channels: Get the low down. J. Neurophysiology 92:2633-2641.

Lipscombe, D. and A. J. Castiglioni (2004). Alternative splicing in voltage gated calcium channels. Calcium Channel Pharmacology. S. I. McDonough. New York, Kluwer Academic/Plenum: 369-409.

Lipscombe, D., T. D. Helton, et al. (2004). "L-type calcium channels: the low down." J Neurophysiol92(5): 2633-41.

Thaler, C., A. C. Gray, et al. (2004). "Cumulative inactivation of N-type CaV2.2 calcium channels modified by alternative splicing." Proc Natl Acad Sci U S A101(15): 5675-9.

Lipscombe, D. (2002). "L-type calcium channels: highs and new lows." Circ Res90(9): 933-5.

Lipscombe, D., J. Q. Pan, et al. (2002). "Functional diversity in neuronal voltage-gated calcium channels by alternative splicing of Ca(v)alpha1." Mol Neurobiol26(1): 21-44.

Xu, W & Lipscombe, D. (2001) Neuronal CaV1.3alpha1 L-type channels activate at relatively hyperpolarized membrane potentials and are incompletely inhibited by dihydropyridines. J. Neuroscience 21:5944-5951.

Lipscombe, D. (2000) "Ion channels". The Encyclopedia of Life Sciences. Macmillan Press.

Pan, JQ & Lipscombe, D (2000). Alternative splicing in the II-III loop of the N-type Ca channel alpha1 subunit: Functional differences are beta-subunit specific. J. Neuroscience 20:4769-4775.