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Modulation of voltage-gated Ca2+ channels in rat retinal ganglion cells by gabapentin

Published online by Cambridge University Press:  23 December 2013

SPRING R. FARRELL ,
ALLISON SARGOY ,
NICHOLAS C. BRECHA  and
STEVEN BARNES
SPRING R. FARRELL
Affiliation:
Department of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia
ALLISON SARGOY
Affiliation:
Department of Neurobiology, David Geffen School of Medicine at the University of California-Los Angeles, Los Angeles, California
NICHOLAS C. BRECHA
Affiliation:
Department of Neurobiology, David Geffen School of Medicine at the University of California-Los Angeles, Los Angeles, California Department of Medicine, Jules Stein Eye Institute, and CURE Digestive Diseases Research Center, David Geffen School of Medicine at the University of California-Los Angeles, Los Angeles, California Veterans Administration Greater Los Angeles Health System, Los Angeles, California
STEVEN BARNES*
Affiliation:
Department of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia Department of Neurobiology, David Geffen School of Medicine at the University of California-Los Angeles, Los Angeles, California Veterans Administration Greater Los Angeles Health System, Los Angeles, California Neuroscience Institute and Department of Ophthalmology and Visual Sciences, Dalhousie University, Halifax, Nova Scotia
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Abstract

The α2δ auxiliary subunits of voltage-gated Ca2+ channels (VGCCs) are important modulators of VGCC function. Gabapentin interacts with α2δ1 and α2δ2 subunits and is reported to reduce Ca2+ channel current amplitude (ICa). This study aimed to determine the effects of gabapentin on VGCCs in retinal ganglion cells (RGCs). Whole cell patch clamp was used to record ICa in isolated RGCs, and calcium imaging was used to measure Ca2+ transients from RGCs in situ. Immunohistochemistry was used to detect the presence of α2δ1-containing VGCCs in isolated RGCs in the absence and presence of gabapentin pretreatment. Acute administration of gabapentin reduced ICa and Ca2+ transients compared to control conditions. In isolated RGCs, pretreatment with gabapentin (4–18 h) reduced ICa, and cell surface α2δ1 staining was reduced compared to nonpretreated cells. Acute administration of gabapentin to isolated RGCs that had been pretreated further reduced ICa. These results show that gabapentin has both short-term and long-term mechanisms to reduce ICa in isolated RGCs. Some Ca2+ channel blockers have been shown to protect RGCs in retinal trauma suggesting that modulation of VGCCs by gabapentin may prevent the deleterious effects of elevated Ca2+ levels in RGCs in trauma and disease.

Keywords

α2δ Ca channel subunitAlpha2delta subunitCacna2d1Retinal ganglion cellGabapentin
Type
Research Articles
Information
Visual Neuroscience , Volume 31 , Issue 1 , January 2014 , pp. 47 - 55
Copyright
Copyright © Cambridge University Press 2013 

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References

Barres, B.A., Silverstein, B.E., Corey, D.P. & Chun, L.L. (1988). Immunological, morphological, and electrophysiological variation among retinal ganglion cells purified by panning. Neuron 1, 791–803.Google Scholar
Bauer, C.S., Nieto-Rostro, M., Rahman, W., Tran-Van-Minh, A., Ferron, L., Douglas, L., Kadurin, I., Sri Ranjan, Y., Fernandez-Alacid, L., Millar, N.S., Dickenson, A.H., Lujan, R. & Dolphin, A.C. (2009). The increased trafficking of the calcium channel subunit alpha2delta-1 to presynaptic terminals in neuropathic pain is inhibited by the alpha2delta ligand pregabalin. The Journal of Neuroscience 29, 4076–4088.Google Scholar
Birnbaumer, L., Qin, N., Olcese, R., Tareilus, E., Platano, D., Costantin, J. & Stefani, E. (1998). Structures and functions of calcium channel beta subunits. Journal of Bioenergetics and Biomembranes 30, 357–375.Google Scholar
Buraei, Z. & Yang, J. (2010). The β subunit of voltage-gated Ca2+ channels. Physiological Reviews 90, 1461–1506.CrossRefGoogle ScholarPubMed
Cole, R.L., Lechner, S.M., Williams, M.E., Prodanovich, P., Bleicher, L., Varney, M.A. & Gu, G. (2005). Differential distribution of voltage-gated calcium channel alpha-2 delta (alpha2delta) subunit mRNA-containing cells in the rat central nervous system and the dorsal root ganglia. The Journal of Comparative Neurology 491, 246–269.CrossRefGoogle ScholarPubMed
Davies, A., Douglas, L., Hendrich, J., Wratten, J., Tran Van Minh, A., Foucault, I., Koch, D., Pratt, W.S., Saibil, H.R. & Dolphin, A.C. (2006). The calcium channel alpha2delta-2 subunit partitions with CaV2.1 into lipid rafts in cerebellum: Implications for localization and function. The Journal of Neuroscience 26, 8748–8757.Google Scholar
Dolphin, A.C. (2009 a). Calcium channel diversity: Multiple roles of calcium channel subunits. Current Opinion in Neurobiology 19, 237–244.CrossRefGoogle ScholarPubMed
Dolphin, A.C. (2009 b). The increased trafficking of the calcium channel subunit alpha2delta-1 to presynaptic terminals in neuropathic pain is inhibited by the alpha2delta ligand pregabalin. The Journal of Neuroscience 29, 4076–4088.Google Scholar
Fehrenbacher, J.C., Taylor, C.P. & Vasko, M.R. (2003). Pregabalin and gabapentin reduce release of substance P and CGRP from rat spinal tissues only after inflammation or activation of protein kinase C. Pain 105, 133–141.Google Scholar
Gee, N.S., Brown, J.P., Dissanayake, V.U., Offord, J., Thurlow, R. & Woodruff, G.N. (1996). The novel anticonvulsant drug, gabapentin (Neurontin), binds to the alpha2delta subunit of a calcium channel. The Journal of Biological Chemistry 271, 5768–5776.Google Scholar
Gerhardstein, B.L., Puri, T.S., Chien, A.J. & Hosey, M.M. (1999). Identification of the sites phosphorylated by cyclic AMP-dependent protein kinase on the beta 2 subunit of L-type voltage-dependent calcium channels. Biochemistry 38, 10361–10370.Google Scholar
Hartwick, A.T., Lalonde, M.R., Barnes, S. & Baldridge, W.H. (2004). Adenosine A1-receptor modulation of glutamate-induced calcium influx in rat retinal ganglion cells. Investigative Ophthalmology & Visual Science 45, 3740–3748.Google Scholar
Heblich, F., Tran Van Minh, A., Hendrich, J., Watschinger, K., Dolphin, A.C. (2008). Time course and specificity of the pharmacological disruption of the trafficking of voltage-gated calcium channels by gabapentin. Channels (Austin) 2, 4–9.CrossRefGoogle ScholarPubMed
Hendrich, J., Van Minh, A.T., Heblich, F., Nieto-Rostro, M., Watschinger, K., Striessnig, J., Wratten, J., Davies, A. & Dolphin, A.C. (2008). Pharmacological disruption of calcium channel trafficking by the alpha2delta ligand gabapentin. Proceedings of the National Academy of Sciences of the United States of America 105, 3628–3633.Google Scholar
Kang, M.G., Felix, R. & Campbell, K.P. (2002). Long-term regulation of voltage-gated Ca(2+) channels by gabapentin. FEBS Letters 528, 177–182.Google Scholar
Koulen, P., Malitschek, B., Kuhn, R., Bettler, B., Wässle, H. & Brandstätter, J.H. (1998). Presynaptic and postsynaptic localization of GABA(B) receptors in neurons of the rat retina. The European Journal of Neuroscience 10, 1446–1456.CrossRefGoogle ScholarPubMed
Li, C.Y., Song, Y.H., Higuera, E.S. & Luo, Z.D. (2004). Spinal dorsal horn calcium channel alpha2delta-1 subunit upregulation contributes to peripheral nerve injury-induced tactile allodynia. The Journal of Neuroscience 24, 8494–8499.CrossRefGoogle ScholarPubMed
Li, C.Y., Zhang, X.L., Matthews, E.A., Li, K.W., Kurwa, A., Boroujerdi, A., Gross, J., Gold, M.S., Dickenson, A.H., Feng, G. & Luo, Z.D. (2006). Calcium channel alpha2delta1 subunit mediates spinal hyperexcitability in pain modulation. Pain 125, 20–34.Google Scholar
Martin, D.J., McClelland, D., Herd, M.B., Sutton, K.G., Hall, M.D., Lee, K., Pinnock, R.D. & Scott, R.H. (2002). Gabapentin-mediated inhibition of voltage-activated Ca2+ channel currents in cultured sensory neurones is dependent on culture conditions and channel subunit expression. Neuropharmacology 42, 353–366.Google Scholar
McClelland, D., Evans, R.M., Barkworth, L., Martin, D.J. & Scott, R.H. (2004). A study comparing the actions of gabapentin and pregabalin on the electrophysiological properties of cultured DRG neurones from neonatal rats. BMC Pharmacology 4, 14.Google Scholar
Mich, P.M. & Horne, W.A. (2008). Alternative splicing of the Ca2+ channel beta4 subunit confers specificity for gabapentin inhibition of Cav2.1 trafficking. Molecular Pharmacology 74, 904–912.Google Scholar
Osborne, N.N., Casson, R.J., Wood, J.P., Chidlow, G., Graham, M. & Melena, J. (2004). Retinal ischemia: Mechanisms of damage and potential therapeutic strategies. Progress in Retinal and Eye Research 23, 91–147.Google Scholar
Rock, D.M., Kelly, K.M. & Macdonald, R.L. (1993). Gabapentin actions on ligand- and voltage-gated responses in cultured rodent neurons. Epilepsy Research 16, 89–98.Google Scholar
Schlick, B., Flucher, B.E. & Obermair, G.J. (2010). Voltage-activated calcium channel expression profiles in mouse brain and cultured hippocampal neurons. Neuroscience 167, 786–798.Google Scholar
Shen, W. & Slaughter, M.M. (1999). Metabotropic GABA receptors facilitate L-type and inhibit N-type calcium channels in single salamander retinal neurons. The Journal of Physiology 516, 711–718.Google Scholar
Stefani, A., Spadoni, F. & Bernardi, G. (1998). Gabapentin inhibits calcium currents in isolated rat brain neurons. Neuropharmacology 37(1), 83–91.Google Scholar
Stefani, A., Spadoni, F., Giacomini, P., Lavaroni, F. & Bernardi, G. (2001). The effects of gabapentin on different ligand- and voltage-gated currents in isolated cortical neurons. Epilepsy Research 43, 239–248.Google Scholar
Suman-Chauhan, N., Webdale, L., Hill, D.R. & Woodruff, G.N. (1993). Characterisation of [3H]gabapentin binding to a novel site in rat brain: Homogenate binding studies. European journal of pharmacology 244, 293–301.Google Scholar
Sutton, K.G., Martin, D.J., Pinnock, R.D., Lee, K. & Scott, R.H. (2002). Gabapentin inhibits high-threshold calcium channel currents in cultured rat dorsal root ganglion neurones. British Journal of Pharmacology 135, 257–265.CrossRefGoogle ScholarPubMed
Uchitel, O.D., Di Guilmi, M.N., Urbano, F.J. & Gonzalez-Inchauspe, C. (2010). Acute modulation of calcium currents and synaptic transmission by gabapentinoids. Channels (Austin) 4, 490–496.Google Scholar
Walker, D. & De Waard, M. (1998). Subunit interaction sites in voltage-dependent Ca2+ channels: Role in channel function. Trends in Neurosciences 21, 148–154.Google Scholar