Advanced SearchSearch Tips
Dual Regulation of R-Type CaV2.3 Channels by M1 Muscarinic Receptors
facebook(new window)  Pirnt(new window) E-mail(new window) Excel Download
  • Journal title : Molecules and Cells
  • Volume 39, Issue 4,  2016, pp.322-329
  • Publisher : Korea Society for Molecular and Cellular Biology
  • DOI : 10.14348/molcells.2016.2292
 Title & Authors
Dual Regulation of R-Type CaV2.3 Channels by M1 Muscarinic Receptors
Jeong, Jin-Young; Kweon, Hae-Jin; Suh, Byung-Chang;
  PDF(new window)
Voltage-gated () channels are dynamically modulated by Gprotein-coupled receptors (GPCR). The muscarinic receptor stimulation is known to enhance channel gating through the activation of protein kinase C (PKC). Here, we found that receptors also inhibit 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 currents by ~two-fold. After the PMA-induced potentiation, stimulation of receptors decreased the currents by . We examined whether the depletion of phosphatidylinositol 4,5-bisphosphate () is responsible for the muscarinic suppression of 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 to phosphatidylinositol 4-phosphate (PI(4)P) by Dr-VSP significantly suppressed currents, by . Next, dephosphorylation of both PI(4)P and to PI by PJ translocation further decreased the current by up to . The results suggest that currents are modulated by the receptor in a dual mode-that is, potentiation through the activation of PKC and suppression by the depletion of membrane . Our results also suggest that there is rapid turnover between PI(4)P and in the plasma membrane.
channel;Danio rerio voltage-sensitive phosphatase(Dr-VSP); muscarinic receptor;;Pseudojanin;
 Cited by
Stimulatory and inhibitory effects of PKC isozymes are mediated by serine/threonine PKC sites of the Ca v 2.3α 1 subunits, Archives of Biochemistry and Biophysics, 2017, 621, 24  crossref(new windwow)
The HOOK region of voltage-gated Ca2+channel β subunits senses and transmits PIP2signals to the gate, The Journal of General Physiology, 2017, 149, 2, 261  crossref(new windwow)
PI(4,5)P 2 and L-type Ca 2+ Channels Partner Up to Fine-Tune Ca 2+ Dynamics in β Cells, Cell Chemical Biology, 2016, 23, 7, 753  crossref(new windwow)
Balla, T. (2013). Phosphoinositides: tiny lipids with giant impact on cell regulation. Physiol. Rev. 93, 1019-1137. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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.

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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.

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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.

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. crossref(new window)

Okamura, Y, Murata, Y., and Iwasaki, H. (2009). Voltage-sensing phosphatase: actions and potentials. J. Physiol. 587(Pt 3), 513-520.

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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.

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. crossref(new window)

Rohacs T. (2009). Phosphoinositide regulation of non-canonical transient receptor potential channels. Cell Calcium 45, 554-565. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

Suh, B.C., and Hille, B. (2005). Regulation of ion channels by phosphatidylinositol 4,5-bisphosphate. Curr. Opin. Neurobiol. 15, 370-378. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)

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.

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. crossref(new window)

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. crossref(new window)

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. crossref(new window)