Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
권호 표지
DOI QR코드

DOI QR Code

Dual Regulation of R-Type CaV2.3 Channels by M1 Muscarinic Receptors

  • Received : 2015.10.20
  • Accepted : 2016.02.05
  • Published : 2016.04.30
Download PDF
⟨ Previous Next ⟩

Abstract

Voltage-gated $Ca^{2+}$ ($Ca_V$) channels are dynamically modulated by Gprotein-coupled receptors (GPCR). The $M_1$ muscarinic receptor stimulation is known to enhance $Ca_V2.3$ channel gating through the activation of protein kinase C (PKC). Here, we found that $M_1$ receptors also inhibit $Ca_V2.3$ currents when the channels are fully activated by PKC. In whole-cell configuration, the application of phorbol 12-myristate 13-acetate (PMA), a PKC activator, potentiated $Ca_V2.3$ currents by ~two-fold. After the PMA-induced potentiation, stimulation of $M_1$ receptors decreased the $Ca_V2.3$ currents by $52{\pm}8%$. We examined whether the depletion of phosphatidylinositol 4,5-bisphosphate ($PI(4,5)P_2$) is responsible for the muscarinic suppression of $Ca_V2.3$ currents by using two methods: the Danio rerio voltage-sensing phosphatase (Dr-VSP) system and the rapamycin-induced translocatable pseudojanin (PJ) system. First, dephosphorylation of $PI(4,5)P_2$ to phosphatidylinositol 4-phosphate (PI(4)P) by Dr-VSP significantly suppressed $Ca_V2.3$ currents, by $53{\pm}3%$. Next, dephosphorylation of both PI(4)P and $PI(4,5)P_2$ to PI by PJ translocation further decreased the current by up to $66{\pm}3%$. The results suggest that $Ca_V2.3$ currents are modulated by the $M_1$ receptor in a dual mode-that is, potentiation through the activation of PKC and suppression by the depletion of membrane $PI(4,5)P_2$. Our results also suggest that there is rapid turnover between PI(4)P and $PI(4,5)P_2$ in the plasma membrane.

Keywords

References

  1. Balla, T. (2013). Phosphoinositides: tiny lipids with giant impact on cell regulation. Physiol. Rev. 93, 1019-1137. https://doi.org/10.1152/physrev.00028.2012
  2. Bannister, R.A., Melliti, K., and Adams, B.A. (2004). Differential modulation of CaV2.3 $Ca6{2+}$ channels by $G{\alpha}_{q/11}$-coupled muscarinic receptors. Mol. Pharmacol. 65, 381-388. https://doi.org/10.1124/mol.65.2.381
  3. Bielas, S.L., Silhavy, J.L., Brancati, F., Kisseleva, M.V., Al-Gazali, L., Sztriha, L., Bayoumi, R.A., Zaki, M.S., Abdel-Aleem, A., Rosti, R.O., et al. (2009). Mutations in INPP5E, encoding inositol polyphosphate- 5-phosphatase E, link phosphatidyl inositol signaling to the ciliopathies. Nat. Genet. 41, 1032-1036. https://doi.org/10.1038/ng.423
  4. Dickson, E.J., Jensen, J.B., and Hille, B. (2014). Golgi and plasma membrane pools of PI(4)P contribute to plasma membrane PI(4,5)$P_2$ and maintenance of KCNQ2/3 ion channel current. Proc. Natl. Acad. Sci. USA 111, E2281-90. https://doi.org/10.1073/pnas.1407133111
  5. Fang, H., Franke, R., Patanavanich, S., Lalvani, A., Powell, N.K., Sando, J.J., and Kamatchi, G.L. (2005). Role of ${\alpha}1$ 2.3 subunit I-II linker sites in the enhancement of $Ca_V2.3$ current by phorbol 12-myristate 13-acetate and acetyl-$\beta$-methylcholine. J. Biol. Chem. 208, 23559-23565.
  6. Gamper, N., Reznikov, V., Yamada, Y., Yang, J., and Shapiro, M.S. (2004). Phosphatidylinositol 4,5-bisphosphate signals underlie receptor-specific $G_{q/11}$-mediated modulation of N-type $Ca^{2+}$ channels. J. Neurosci. 24, 10980-10992. https://doi.org/10.1523/JNEUROSCI.3869-04.2004
  7. Guo, S., Stolz, L.E., Lemrow, S.M., and York, J.D. (1999). SAC1- like domains of yeast SAC1, INP52, and INP53 and of human synaptojanin encode polyphosphoinositide phosphatases. J. Biol. Chem. 274, 12990-12995. https://doi.org/10.1074/jbc.274.19.12990
  8. Hamid, J., Nelson, D., Spaetgens, R., Dubel, S.J., Snutch, T.P., and Zamponi, G.W. (1999). Identification of an integration center for cross-talk between protein kinase C and G protein modulation of N-type calcium channels. J. Biol. Chem. 274, 6195-6202. https://doi.org/10.1074/jbc.274.10.6195
  9. Hammond, G.R., Fischer, M.J., Anderson, K.E., Holdich, J., Koteci, A., Balla, T., and Irvine, R.F. (2012). PI4P and $PI(4,5)P_2$ are essential but independent lipid determinants of membrane identity. Science 337, 727-730. https://doi.org/10.1126/science.1222483
  10. Hilgemann, D.W., Feng, S., and Nasuhoglu, C. (2001). The complex and intriguing lives of $PIP_2$ with ion channels and transporters. Sci. STKE 2001, re19.
  11. Huang, C.L. (2007). Complex roles of $PIP_2$ in the regulation of ion channels and transporters. Am. J. Physiol. Renal Physiol. 293, F1761-F1765. https://doi.org/10.1152/ajprenal.00400.2007
  12. Inoue, T., Heo, W.D., Grimley, J.S., Wandless, T.J., and Meyer, T. (2005). An inducible translocation strategy to rapidly activate and inhibit small GTPase signaling pathways. Nat. Methods 2, 415-418. https://doi.org/10.1038/nmeth763
  13. Kamatchi, G.L., Tiwari, S.N., Chan, C.K., Chen, D., Do, S.H., Durieux M.E., and Lynch C. 3rd. (2003). Distinct regulation of expressed calcium channels 2.3 in Xenopus oocytes by direct or indirect activation of protein kinase C. Brain Res. 968, 227-237. https://doi.org/10.1016/S0006-8993(03)02245-5
  14. Kamatchi, G.L., Franke, R., Lynch, C. 3rd, and Sando, J.J. (2004). Identification of sites responsible for potentiation of type 2.3 calcium currents by acetyl-$\beta$-methylcholine. J. Biol. Chem. 279, 4102-4109. https://doi.org/10.1074/jbc.M308606200
  15. Kammermeier, P.J., Ruiz-Velasco, V., and Ikeda, S.R. (2000). A voltage-independent calcium current inhibitory pathway activated by muscarinic agonists in rat sympathetic neurons requires both $G{\alpha}_{q/11}$ and $G{\beta}{\gamma}$. J. Neurosci. 20, 5623-5629. https://doi.org/10.1523/JNEUROSCI.20-15-05623.2000
  16. Keum, D., Baek, C., Kim, D.I., Kweon, H.J., and Suh, B.C. (2014). Voltage-dependent regulation of $Ca_V2.2$ channels by $G_q$-coupled receptor is facilitated by membrane-localized $\beta$ subunit. J. Gen. Physiol. 144, 297-309. https://doi.org/10.1085/jgp.201411245
  17. Kim, D.I., Park, Y., Jang, D.J., and Suh, B.C. (2015). Dynamic phospholipid interaction of ${\beta}2e$ subunit regulates the gating of voltage-gated $Ca^{2+}$ channels. J. Gen. Physiol. 145, 529-541. https://doi.org/10.1085/jgp.201411349
  18. Kwiatkowska, K. (2010). One lipid, multiple functions: how various pools of PI(4,5)$P_2$ are created in the plasma membrane. Cell. Mol. Life Sci. 67, 3927-3946. https://doi.org/10.1007/s00018-010-0432-5
  19. Lee, S.C., Choi, S., Lee, T., Kim, H.L., Chin, H., and Shin, H.S. (2002) Molecular basis of R-type calcium channels in central amygdala neurons of the mouse. Proc. Natl. Acad. Sci. USA 99, 3276-3281. https://doi.org/10.1073/pnas.052697799
  20. Liang, H., DeMaria, C.D., Erickson, M.G., Mori, M.X., Alseikhan, B.A., and Yue, D.T. (2003). Unified mechanisms of $Ca^{2+}$ regulation across the $Ca^{2+}$ channel family. Neuron 39, 951-960. https://doi.org/10.1016/S0896-6273(03)00560-9
  21. Melliti, K., Meza, U., and Adams, B. (2000). Muscarinic stimulation of ${\alpha}1E$ Ca channels is selectively blocked by the effector antagonist function of RGS2 and phospholipase C-${\beta}1$. J. Neurosci. 20, 7167-7173. https://doi.org/10.1523/JNEUROSCI.20-19-07167.2000
  22. Melliti, K., Meza, U., and Adams, B.A. (2001). RGS2 blocks slow muscarinic inhibition of N-type $Ca^{2+}$ channels reconstituted in a human cell line. J. Physiol. 532, 337-347. https://doi.org/10.1111/j.1469-7793.2001.0337f.x
  23. Meza, U., Thapliyal, A., Bannister, R.A., and Adams, B.A. (2007). Neurokinin 1 receptors trigger overlapping stimulation and inhibition of $Ca_V2.3$ (R-type) calcium channels. Mol. Pharmacol. 71, 284-293.
  24. Niidome, T., Kim, M.S., Friedrich, T., and Mori, Y. (1992). Molecular cloning and characterization of a novel calcium channel from rabbit brain. FEBS Lett. 308, 7-13. https://doi.org/10.1016/0014-5793(92)81038-N
  25. Okamura, Y, Murata, Y., and Iwasaki, H. (2009). Voltage-sensing phosphatase: actions and potentials. J. Physiol. 587(Pt 3), 513-520.
  26. Oude Weernink, P.A., Schmidt, M., and Jakobs, K.H. (2004). Regulation and cellular roles of phosphoinositide 5-kinases. Eur. J. Pharmacol. 500, 87-99. https://doi.org/10.1016/j.ejphar.2004.07.014
  27. Page, K.M., Cantí, C., Stephens, G.J., Berrow, N.S., and Dolphin, A.C. (1998). Identification of the amino terminus of neuronal $Ca^{2+}$ channel ${\alpha}1$ subunits $\alpha$ 1B and ${\alpha}1E$ as an essential determinant of G-protein modulation. J. Neurosci. 18, 4815-4824. https://doi.org/10.1523/JNEUROSCI.18-13-04815.1998
  28. Perez-Burgos, A., Perez-Rosello, T., Salgado, H., Flores-Barrera, E., Prieto, G.A., Fugueroa, A., Galarraga, E., and Bargas, J. (2008). Muscarinic M1 modulation of N- and L-types of calcium channels is mediated by protein kinase C in neostriatal neurons. Neuroscience 155, 1079-1097. https://doi.org/10.1016/j.neuroscience.2008.06.047
  29. Perez-Burgos, A., Prieto, G.A., Galarraga, E., and Bargas, J. (2010). $Ca_V2.1$ channels are modulated by muscarinic $M_1$ receptors through phosphoinositied hydrolysis in neostriatal neurons. Neuroscience 165, 293-299. https://doi.org/10.1016/j.neuroscience.2009.10.056
  30. Perez-Rosello, T., Figueroa, A., Salgado, H., Vilchis, C., Tecuapetia, F., Guzman, J.N., Galarraga, E., and Bargas, J. (2004). Cholinergic control of firing pattern and neurotransmission in rat neostriatal projection neurons: role of $Ca_V2.1$ and $Ca_V2.2$ $Ca^{2+}$ channels. J. Neurophysiol. 93, 2507-2519.
  31. Rajagopal, S., Fang, H., Patanavanich, S., Sando, J.J., and Kamatchi, G.L. (2008). Protein kinase C isozyme-specific potentiation of expressed $Ca_V2.3$ currents by acetyl-$\beta$-methylcholine and phorbol- 12-myristate, 13-acetate. Brain Res. 1210, 1-10. https://doi.org/10.1016/j.brainres.2008.03.017
  32. Rohacs T. (2009). Phosphoinositide regulation of non-canonical transient receptor potential channels. Cell Calcium 45, 554-565. https://doi.org/10.1016/j.ceca.2009.03.011
  33. Saequsa, H., Kurihara, T., Zong, S., Minowa, O., Kazuno, A., Han, W., Matsuda, Y., Yamanaka, H., Osanai, M., Noda, T., et al. (2000). Altered pain responses in mice lacking ${\alpha}1E$ subunit of the voltage-dependent $Ca^{2+}$ channel. Proc. Natl. Acad. Sci. USA 97, 6132-6137. https://doi.org/10.1073/pnas.100124197
  34. Shapiro, M.S., Loose, M.D., Hamilton, S.E., Nathanson, N.M., Gomeza, J., Wess, J., and Gille, B. (1999). Assignment of muscarinic receptor subtypes mediating G-protein modulation of $Ca^{2+}$ channels by using knockout mice. Proc. Natl. Acad. Sci. USA 96, 10899-10904. https://doi.org/10.1073/pnas.96.19.10899
  35. Soong, T.W., Stea, A., Hodson, C.D., Dubel, S.J., Vincent, S.R., and Snutch, T.P. (1993). Structure and functional expression of a member of the low voltage-activated calcium channel family. Science 260, 1133-1136. https://doi.org/10.1126/science.8388125
  36. Stea, A., Soong, T.W., and Snutch, T.P. (1995). Determinants of PKC-dependent modulation of a family of neuronal calcium channels. Neuron 15, 929-940. https://doi.org/10.1016/0896-6273(95)90183-3
  37. Suh, B.C., and Hille, B. (2005). Regulation of ion channels by phosphatidylinositol 4,5-bisphosphate. Curr. Opin. Neurobiol. 15, 370-378. https://doi.org/10.1016/j.conb.2005.05.005
  38. Suh, B.C., and Hille, B. (2008). $PIP_2$ is a necessary cofactor for ion channel function: How and why? Annu. Rev. Biophys. 37, 175-195. https://doi.org/10.1146/annurev.biophys.37.032807.125859
  39. Suh, B.C., Inoue, T., Meyer, T., and Hille, B. (2006). Rapid chemically induced changes of PtdIns(4,5)$P_2$ gate KCNQ ion channels. Science 314, 1454-1457. https://doi.org/10.1126/science.1131163
  40. Suh, B.C., Leal, K., and Hille, B. (2010). Modulation of high-voltage activated $Ca^{2+}$ channels by membrane phosphatidylinositol 4,5-bisphosphate. Neuron 67, 224-238. https://doi.org/10.1016/j.neuron.2010.07.001
  41. Suh, B.C., Kim, D.I., Falkenburger, B.H., and Hille, B. (2012). Membrane-localized $\beta$-subunits alter the $PIP_2$ regulation of highvoltage activated $Ca^{2+}$ channels. Proc. Natl. Acad. Sci. USA 109, 3161-3166. https://doi.org/10.1073/pnas.1121434109
  42. Tai, C., Kuzmiski, J.B., and MacVicar, B.A. (2006). Muscarinic enhancement of R-type calcium currents in hippocampal CA1 pyramidal neurons. J. Neurosci. 26, 6249-6258. https://doi.org/10.1523/JNEUROSCI.1009-06.2006
  43. Williams, M.E., Marubio, L.M., Deal, C.R., Hans, M., Brust P.F., Philipson L.H., Miller R.J., Johnson E.C., Harpold M.M., and Ellis S.B. (1994). Structure and functional characterization of neuronal ${\alpha}1E$ channel subtypes. J. Biol. Chem. 269, 22347-22357.
  44. Wu, L.G., Borst, J.G., and Sakmann, B. (1998). R-type $Ca^{2+}$ currents evoke transmitter release at a rat central synapse. Proc. Natl. Acad. Sci. USA 95, 4720-4725. https://doi.org/10.1073/pnas.95.8.4720
  45. Wuttke, A., Sågetorp, J., and Tengholm, A. (2010). Distinct plasmamembrane PtdIns(4)P and PtdIns(4,5)$P_2$ dynamics in secretagogue- stimulated $\beta$-cells. J. Cell Sci. 123, 1492-1502. https://doi.org/10.1242/jcs.060525
  46. Zamponi, G.W., Bourinet, E., Nelson, D., Nargeot, J., and Snutch, T.P. (1997). Crosstalk between G proteins and protein kinase C mediated by the calcium channel ${\alpha}1$ subunit. Nature 385, 442-446. https://doi.org/10.1038/385442a0

Cited by

  1. Stimulatory and inhibitory effects of PKC isozymes are mediated by serine/threonine PKC sites of the Ca v 2.3α 1 subunits vol.621, 2017, https://doi.org/10.1016/j.abb.2017.04.002
  2. The HOOK region of voltage-gated Ca2+channel β subunits senses and transmits PIP2signals to the gate vol.149, pp.2, 2017, https://doi.org/10.1085/jgp.201611677
  3. PI(4,5)P 2 and L-type Ca 2+ Channels Partner Up to Fine-Tune Ca 2+ Dynamics in β Cells vol.23, pp.7, 2016, https://doi.org/10.1016/j.chembiol.2016.07.001
  4. channel β subunits in α1–β complexes reveal competitive replacement yet no spontaneous dissociation vol.115, pp.42, 2018, https://doi.org/10.1073/pnas.1809762115
  5. 2.3 channels vol.150, pp.3, 2018, https://doi.org/10.1085/jgp.201711880
  6. Voltage-Sensing Phosphatases: Biophysics, Physiology, and Molecular Engineering vol.98, pp.4, 2018, https://doi.org/10.1152/physrev.00056.2017
  7. Phospholipids of Synaptic Membranes in the Pathogenesis of Encephalopathy During Hemorrhagic Shock (Review) vol.15, pp.2, 2016, https://doi.org/10.15360/1813-9779-2019-2-99-114
  8. Differential Regulation of Ca2+-Activated Cl− Channel TMEM16A Splice Variants by Membrane PI(4,5)P2 vol.22, pp.8, 2021, https://doi.org/10.3390/ijms22084088