Formalin-Induced Short- and Long-Term Modulation of Cav Currents Expressed in Xenopus Oocytes: An In Vitro Cellular Model for Formalin-Induced Pain
Senthilkumar Rajagopal,
Hongyu Fang,
Carl Lynch III,
Ganesan L. Kamatchi,
Senthilkumar Rajagopal
Department of Anesthesiology, University of Virginia, Charlottesville, VA, USA
Search for more papers by this authorHongyu Fang
Department of Anesthesiology, University of Virginia, Charlottesville, VA, USA
Search for more papers by this authorCarl Lynch III
Department of Anesthesiology, University of Virginia, Charlottesville, VA, USA
Search for more papers by this authorGanesan L. Kamatchi
Department of Anesthesiology, University of Virginia, Charlottesville, VA, USA
Search for more papers by this authorSenthilkumar Rajagopal,
Hongyu Fang,
Carl Lynch III,
Ganesan L. Kamatchi,
Senthilkumar Rajagopal
Department of Anesthesiology, University of Virginia, Charlottesville, VA, USA
Search for more papers by this authorHongyu Fang
Department of Anesthesiology, University of Virginia, Charlottesville, VA, USA
Search for more papers by this authorCarl Lynch III
Department of Anesthesiology, University of Virginia, Charlottesville, VA, USA
Search for more papers by this authorGanesan L. Kamatchi
Department of Anesthesiology, University of Virginia, Charlottesville, VA, USA
Search for more papers by this authorAuthor for correspondence: Ganesan L. Kamatchi, Department of Biology, Norfolk State University, 700 Park Avenue, Norfolk, VA 23504, USA (fax: +1 757 823 2286, e-mail [email protected]).
Present address: Senthilkumar Rajagopal, Department of Cancer immunology & AIDS, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Present address: Hongyu Fang, Department of Anesthesiology, Froedtert and the Medical College of Wisconsin, 9200 W Wisconsin Ave., Milwaukee, WI 53226, USA.
Abstract
Abstract: Xenopus oocytes expressing high voltage-gated calcium channels (Cav) were exposed to formalin (0.5%, v/v, 5 min.) and the oocyte death and Cav currents were studied for up to 10 days. Cav channels were expressed with α1β1b and α2δ sub-units and the currents (IBa) were studied by voltage clamp. None of the oocytes was dead during the exposure to formalin. Oocyte death was significant between day 1 and day 5 after the exposure to formalin and was uniform among the oocytes expressing various Cav channels. Peak IBa of all Cav and A1, the inactivating current component was decreased whereas the non-inactivated R current was not affected by 5 min. exposure to formalin. On day 1 after the exposure to formalin, Cav1.2c currents were increased, 2.1 and 2.2 currents were decreased and 2.3 currents were unaltered. On day 5, both peak IBa and A1 currents were increased. Cav1.2c, 2.2 and 2.3 currents were increased and Cav2.1 was unaltered on day 10 after the exposure to formalin. Protein kinase C (PKC) may be involved in formalin-induced increase in Cav currents due to the (i) requirement for Cavβ1b sub-units; (ii) decreased phorbol-12-myristate,13-acetate potentiation of Cav2.3 currents; (iii) absence of potentiation of Cav2.3 currents following down-regulation of PKC; and (iv) absence of potentiation of Cav2.2 or 2.3 currents with Ser→Ala mutation of Cavα12.2 or 2.3 sub-units. Increased Cav currents and PKC activation may coincide with changes observed in in vivo pain investigations, and oocytes incubated with formalin may serve as an in vitro model for some cellular mechanisms of pain.
References
- 1 Okabe K, Terada K, Kitamura K, Kuriyama H. Selective and long-lasting inhibitory actions of the dihydropyridine derivative, CV-4093, on calcium currents in smooth muscle cells of the rabbit pulmonary artery. J Pharmacol Exp Ther 1987; 243: 703–10.
- 2 Endoh M, Hiramoto T, Ishihata A, Takanashi M, Inui J. Myocardial α1-adrenoceptors mediate positive inotropic effect and changes in phosphatidylinositol metabolism: species differences in receptor distribution and the intracellular coupling process in mammalian ventricular myocardium. Circ Res 1991; 68: 1179–90.
- 3 Hunt S, Mantyh P. The molecular dynamics of pain control. Nature Rev Neurosci 2001; 2: 83–91.
- 4 Krarup C. An update on electrophysiological studies in neuropathy. Curr Opin Neurol 2003; 16: 603–12.
- 5 Ueda H. Molecular mechanisms of neuropathic pain-phenotypic switch and initiation mechanisms. Pharmacol Ther 2006; 109: 57–77.
- 6 Walker D, De Waard M. Subunit interaction sites in voltage-dependent Ca2+ channels: role in channel function. Trends NeuroSci 1998; 21: 148–54.
- 7 Jones L, Wei S-K, Yue D. Mechanism of auxiliary subunit modulation of neuronal alpha 1E calcium channels. J Gen Physiol 1998; 112: 125–43.
- 8 Sheng Z-H, Rettig J, Takahashi M, Catterall WA. Identification of a syntaxin-binding site on N-type calcium channels. Neuron 1994; 13: 1303–13.
- 9 Rettig J, Sheng Z-H, Kim DK, Hodson CD, Snutch TP. Isoform-specific interaction of the α1A subunits of brain Ca2+ channels with the presynaptic proteins syntaxin and SNAP-25. Proc Natl Acad Sci U S A 1996; 93: 7363–8.
- 10 Sheng Z-H, Rettig J, Cook T, Catterall W. Calcium-dependent interaction of N-type calcium channels with the synaptic core-complex. Nature 1996; 379: 451–4.
- 11 Coderre T, Katz J, Vaccarino A, Melzack R. Contribution of central neuroplasticity to pathological pain: review of clinical and experimental evidence. Pain 1993; 52: 259–85.
- 12 Yaksh TL. Central pharmacology of nociceptive transmission. In: PD Wall, R Melzack (eds). Textbook of Pain. Churchill Livingstone, London, UK, 1999; 253–308.
- 13 Newton A, Johnson J. Protein kinase C: a paradigm for regulation of protein function by two membrane-targeting modules. Biochim Biophys Acta 1998; 1376: 155–72.
- 14 Guenther S, Reeh P, Kress M. Rises in [Ca2+]i mediate capsaicin- and proton-induced heat sensitization of rat primary nociceptive neurons. Eur J Neurosci 1999; 11: 3143–50.
- 15 Shistik E, Keren-Raifman T, Idelson G, Blumenstein Y, Dascal N, Ivanina T. The N terminus of the cardiac L-type Ca2+ channel α1c subunit. J Biol Chem 1999; 274: 31145–9.
- 16 McHugh D, Sharp E, Scheuer T, Catterall W. Inhibition of cardiac L-type calcium channels by protein kinase C phosphorylation of two sites in the N-terminal domain. Proc Natl Acad Sci U S A 2000; 97: 12334–8.
- 17 Kamatchi G, Franke R, Lynch C III, Sando J. Identification of sites responsible for potentiation of type 2.3 calcium currents by acetyl-β-methylcholine. J Biol Chem 2004; 279: 4102–9.
- 18 Fang H, Franke R, Patanavanich S, Lalvani A, Powell N, Sando J et al. Role of α1 2.3 subunit I-II linker sites in the enhancement of Cav 2.3 currents by phorbol 13-myristate,13-acetate. J Biol Chem 2005; 280: 23559–65.
- 19 Fang H, Patanavanich S, Rajagopal S, Yi X, Gill M, Sando J et al. Inhibitory role of Ser-425 of the alpha1 2.2 subunit in the enhancement of Cav2.2 currents by phorbol-12-myristate,13-acetate. J Biol Chem 2006; 281: 20011–7.
- 20 Yokoyama CT, Westenbroek RE, Hell JW, Soong TW, Snutch TP, Catterall WA. Biochemical properties and subcellular distribution of the neuronal class E calcium channel α1 subunit. J Neurosci 1995; 15: 6419–32.
- 21 Puri T, Gerhardstein B, Zhao X-L, Ladner M, Hosey M. Differential effects of subunit interactions on protein kinase A- and C-mediated phosphorylation of L-type calcium channels. Biochemistry 1997; 36: 9605–15.
- 22 Catterall WA. Structure and regulation of voltage-gated Ca2+ channels. Annu Rev Cell Dev Biol 2000; 16: 521–55.
- 23 Catterall W, Hulme J, Jiang X, Few W. Regulation of sodium and calcium channels by signaling complexes. J Recept Signal Transduct Res 2006; 26: 577–98.
- 24 Diaz A, Dickenson A. Blockade of spinal N-and P-type, but not L-type, calcium channels inhibits the excitability of rat dorsal horn neurons produced by subcutaneous formalin inflammation. Pain 1999; 69: 93–100.
- 25 Hagiwara K, Nakagawasai O, Murata A, Yamadera F, Miyoshi I, Tan-No K et al. Analgesic action of loperamide, an opioid agonist, and its blocking action on voltage-dependent Ca2+ channels. Neurosci Res 2003; 46: 493–7.
- 26 Ji R-R, Rupp F. Phosphorylation of transcription factor CREB in rat spinal cord after formalin-induced hyperalgesia: relationship to c-fos induction. J Neurosci 1997; 17: 1776–85.
- 27 Ji R-R, Baba H, Brenner G, Woolf C. Nociceptive-specific activation of ERK in spinal neurons contributes to pain hypersensitivity. Nat Neurosci 1999; 2: 1114–9.
- 28 Dascal N. The use of Xenopus oocytes for the study of ion channels. Crit Rev Biochem Mol 1987; 22: 317–87.
- 29 Snutch TP. The use of Xenopus oocytes to probe synaptic communication. Trends Neurosci 1988; 11: 250–6.
- 30 Lin Z, Haus S, Edgerton J, Lipscombe D. Identification of functionally distinct isoforms of the N-type Ca2+ channel in rat sympathetic ganglia and brain. Neuron 1997; 18: 153–66.
- 31 Kamatchi G, Tiwari S, Chan C, Chen D, Do S-H, Durieux M et al. Distinct regulation of expressed calcium channel 2.3 in Xenopus oocytes by direct or indirect activation of protein kinase C. Brain Res 2003; 968: 227–37.
- 32 Zhou W, Fontenot HJ, Liu S, Kennedy RH. Modulation of cardiac calcium channels by propofol. Anesthesiology 1997; 86: 670–5.
- 33 Stea A, Soong TW, Snutch TP. Voltage-gated calcium channels. In: AR North (ed.). Ligand- and Voltage-Gated Ion Channels. CRC Press Inc., Boca Raton, FL, 1995; 113–52.
- 34 Bancroft J, Gamble M. Reversibility of formalin: macromolecular reactions. In: J Bancroft, M Gamble (eds). Theory and Practice of Histological Techniques. Elsevier Health Sciences, Philadelphia, PA, 2008; 57–9.
- 35 Malorny G, Rietbrock N, Schneider M. Oxidation of formaldehyde to formic acid in blood, a contribution to the metabolism of formaldehyde. Arch Exp Pathol Pharmacol 1965; 250: 419–36.
- 36 McMartin K, Martin-Amat G, Noker P, Tephly T. Lack of role for formaldehyde in methanol poisoning in the monkey. Biochem Pharmacol 1979; 28: 645–9.
- 37 Rietbrock N. Kinetics and pathways of methanol metabolism. Arch Exp Pathol Pharmacol 1969; 263: 88–105.
- 38 Carli G, Montesano A, Rapezzi S, Paluffi G. Differential effects of persistent nociceptive stimulation on sleep stages. Behav Brain Res 1987; 26: 89–98.
- 39 Porro C, Cavazzuti M. Spatial and temporal aspects of spinal cord and brainstem activation in the formalin pain model. Prog Neurobiol 1993; 41: 565–607.
- 40 Farabollini F, Gioroano G, Carli G. Tonic pain and social behavior in male rabbits. Behav Brain Res 1988; 31: 169–75.
- 41 Rajagopal S, Fang H, Patanavanich S, Sando J, Kamatchi GL. Protein kinase C isozyme-specific potentiation of expressed Cav 2.3 currents by acetyl-β-methylcholine and phorbol-12-myristate,13-acetate. Brain Res 2008; 1210: 1–10.
- 42 Castellano A, Wei X, Birnbaumer L, Perez-Reyes E. Cloning and expression of a third calcium channel β subunit. J Biol Chem 1993; 268: 3450–5.
- 43 Castellano A, Wei X, Birnbaumer L, Perez-Reyes E. Cloning and expression of a neuronal calcium channel beta subunit. J Biol Chem 1993; 268: 12359–6.
- 44 Chen C-C. Protein kinase C α, δ, ε and ζ in C6 glioma cells; TPA translocation and down-regulation of conventional and new PKC isoforms but not atypical PKC ζ. FEBS Lett 1993; 332: 169–73.
- 45 Huang L. Calcium channels in isolated rat dorsal horn neurones, including labelled spinothalamic and trigeminothalamic cells. J Physiol 1989; 411: 161–7.
- 46 Ryu P, Randic M. Low- and high-voltage-activated calcium currents in rat spinal dorsal horn neurones. J Neurophysiol 1990; 63: 273–85.
- 47 Westenbroek RE, Hoskins L, Catterall WA. Localization of Ca2+ channels subtypes on rat spinal motor neurons, interneurons and nerve terminals. J Neurosci 1998; 18: 6319–30.
- 48 Saegusa H, Kurihara T, Zong S, Minowa O, Kazuno A, Han W et al. Altered pain responses in mice lacking alpha 1E subunit of the voltage-dependent Ca2+ channel. Proc Natl Acad Sci U S A 2000; 97: 6132–7.
- 49 Cizkova D, Marsala J, Lukacova N, Marsala M, Jergova S, Orendacova J et al. Localization of N-type Calcium channels in the rat spinal cord following chronic constrictive nerve injury. Exp Brain Res 2002; 147: 456–63.
- 50 Chaplan S, Pogrel J, Yaksh TL. Role of voltage-dependent calcium channel subtypes in experimental tactile allodynia. J Pharmacol Exptl Ther 1994; 269: 1117–23.
- 51 White D, Cousins M. Effect of subcutaneous administration of calcium channel blockers on nerve injury-induced hyperalgesia. Brain Res 1998; 801: 50–8.
- 52 Yajima Y, Narita M, Shimamura M, Narita M, Kubota C, Suzuki T. Differential involvement of spinal protein kinase C and protein kinase A in neuropathic and inflammatory pain in mice. Brain Res 2003; 992: 288–93.
- 53 Narita M, Oe K, Kato H, Shibasaki M, Narita M, Yajima Y et al. Implication of spinal protein kinase C in the suppression of morphine-induced rewarding effect under a neuropathic pain-like state in mice. Neuroscience 2004; 125: 545–51.
- 54 Zhou Y, Zhou Z-S, Zhao Z-Q. PKC regulates capsaicin-induced currents of dorsal root ganglion neurons in rats. Neuropharmacology 2001; 41: 601–8.
- 55 Frayer S, Barber L, Vasko M. Activation of protein kinase C enhances peptide release from rat spinal cord slices. Neurosci Lett 1999; 265: 17–20.
- 56 Chuang H, Prescott E, Kong H, Shields S, Jordt S, Basbaum A et al. Bradykinin and nerve growth factor release the capsaicin receptor from PtdIns(4,5)P2-mediated inhibition. Nature 2001; 411: 957–62.
- 57 Cesare P, Dekker L, Sardini A, Parker P, McNaughton P. Specific involvement of PKC-epsilon in sensitization of the neuronal response to painful heat. Neuron 1999; 23: 617–24.
- 58 Vellani V, Mapplebeck S, Moriondo A, Davis J, McNaughton P. Protein kinase C activation potentiates gating of the vanilloid receptor VR1 by capsaicin, protons, heat and anandamide. J Physiol 2001; 534: 813–25.
- 59 Da Cunha J, Rae G, Ferreira S, Cunha F. Endothelins induce ETB receptor-mediated mechanical hypernociception in rat hindpaw: roles of cAMP and protein kinase C. Eur J Pharmacol 2004; 501: 87–94.
- 60 Lin Y, Jover-Mengual T, Wong J, Bennett M, Zukin S. PSD-95 and PKC converge in regulating NMDA receptor trafficking and gating. Proc Natl Acad Sci U S A 2006; 103: 19902–7.
- 61 Lan J, Skeberdis V, Jover T, Grooms S, Lin Y, Araneda R et al. Protein kinase C modulates NMDA receptor trafficking and gating. Nature 2001; 4: 382–90.
- 62 Fields A, Frederick L, Regala R. Targeting the oncogenic protein kinase Ciota signalling pathway for the treatment of cancer. Biochem Soc Trans 2007; 35: 996–100.
- 63 Vignot S, Soria J, Spano J, Mounier N. Protein kinases C: a new cytoplasmic target. Bull Cancer 2008; 95: 683–9.
- 64 Fields A, Murray N. Protein kinase C isozymes as therapeutic targets for treatment of human cancers. Adv Enzyme Regul 2008; 48: 166–78.
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