Caveolin-1 Expression and Membrane Cholesterol Content Modulate N-type Calcium Channel Activity in NG108-15 Cells

Overview

Journal Biophys J

Publisher Cell Press

Specialty Biophysics

Date 2005 Jul 26

PMID 16040758

Citations 46

Authors

M Toselli

G Biella

V Taglietti

E Cazzaniga

M Parenti

Affiliations

Soon will be listed here.

Abstract

Caveolins are the main structural proteins of glycolipid/cholesterol-rich plasmalemmal invaginations, termed caveolae. In addition, caveolin-1 isoform takes part in membrane remodelling as it binds and transports newly synthesized cholesterol from endoplasmic reticulum to the plasma membrane. Caveolin-1 is expressed in many cell types, including hippocampal neurons, where an abundant SNAP25-caveolin-1 complex is detected after induction of persistent synaptic potentiation. To ascertain whether caveolin-1 influences neuronal voltage-gated Ca2+ channel basal activity, we stably expressed caveolin-1 into transfected neuroblastoma x glioma NG108-15 hybrid cells [cav1(+) clone] that lack endogenous caveolins but express N-type Ca2+ channels upon cAMP-induced neuronal differentiation. Whole-cell patch-clamp recordings of cav1(+) cells demonstrated that N-type current density was reduced in size by approximately 70% without any significant change in the time course of activation and inactivation and voltage dependence. Moreover, the cav1(+) clone exhibited a significantly increased proportion of membrane cholesterol compared to wild-type NG108-15 cells. To gain insight into the mechanism underlying caveolin-1 lowering of N-current density, and more precisely to test whether this was indirectly caused by caveolin-1-induced enhancement of membrane cholesterol, we compared single N-type channel activities in cav1(+) clone and wild-type NG108-15 cells enriched with cholesterol after exposure to a methyl-beta-cyclodextrin-cholesterol complex. A lower Ca2+ channel activity was recorded from cell-attached patches of both cell types, thus supporting the view that the increased proportion of membrane cholesterol is ultimately responsible for the effect. This is due to a reduction in the probability of channel opening caused by a significant decrease of channel mean open time and by an increase of the frequency of null sweeps.

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References

Martens J, Navarro-Polanco R, Coppock E, Nishiyama A, Parshley L, Grobaski T . Differential targeting of Shaker-like potassium channels to lipid rafts. J Biol Chem. 2000; 275(11):7443-6. DOI: 10.1074/jbc.275.11.7443. View

Jennings L, Xu Q, Firth T, Nelson M, Mawe G . Cholesterol inhibits spontaneous action potentials and calcium currents in guinea pig gallbladder smooth muscle. Am J Physiol. 1999; 277(5):G1017-26. DOI: 10.1152/ajpgi.1999.277.5.G1017. View

Braun J, Madison D . A novel SNAP25-caveolin complex correlates with the onset of persistent synaptic potentiation. J Neurosci. 2000; 20(16):5997-6006. PMC: 6772581. View

Bucci M, Gratton J, Rudic R, Acevedo L, Roviezzo F, Cirino G . In vivo delivery of the caveolin-1 scaffolding domain inhibits nitric oxide synthesis and reduces inflammation. Nat Med. 2000; 6(12):1362-7. DOI: 10.1038/82176. View

Tong Y, Brandt G, Li M, Shapovalov G, Slimko E, Karschin A . Tyrosine decaging leads to substantial membrane trafficking during modulation of an inward rectifier potassium channel. J Gen Physiol. 2001; 117(2):103-18. PMC: 2217249. DOI: 10.1085/jgp.117.2.103. View

Carabelli V, Hernandez-Guijo J, Baldelli P, Carbone E . Direct autocrine inhibition and cAMP-dependent potentiation of single L-type Ca2+ channels in bovine chromaffin cells. J Physiol. 2001; 532(Pt 1):73-90. PMC: 2278521. DOI: 10.1111/j.1469-7793.2001.0073g.x. View

Martens J, Sakamoto N, Sullivan S, Grobaski T, Tamkun M . Isoform-specific localization of voltage-gated K+ channels to distinct lipid raft populations. Targeting of Kv1.5 to caveolae. J Biol Chem. 2000; 276(11):8409-14. DOI: 10.1074/jbc.M009948200. View

Toselli M, Taglietti V, Parente V, Flati S, Pavan A, Guzzi F . Attenuation of G protein-mediated inhibition of N-type calcium currents by expression of caveolins in mammalian NG108-15 cells. J Physiol. 2001; 536(Pt 2):361-73. PMC: 2278875. DOI: 10.1111/j.1469-7793.2001.0361c.xd. View

Calabrese B, Tabarean I, Juranka P, Morris C . Mechanosensitivity of N-type calcium channel currents. Biophys J. 2002; 83(5):2560-74. PMC: 1302342. DOI: 10.1016/S0006-3495(02)75267-3. View

10.

Hajdu P, Varga Z, Pieri C, Panyi G, Gaspar Jr R . Cholesterol modifies the gating of Kv1.3 in human T lymphocytes. Pflugers Arch. 2003; 445(6):674-82. DOI: 10.1007/s00424-002-0974-y. View

11.

Christian A, Haynes M, Phillips M, Rothblat G . Use of cyclodextrins for manipulating cellular cholesterol content. J Lipid Res. 1997; 38(11):2264-72. View

12.

Okamoto T, Schlegel A, Scherer P, Lisanti M . Caveolins, a family of scaffolding proteins for organizing "preassembled signaling complexes" at the plasma membrane. J Biol Chem. 1998; 273(10):5419-22. DOI: 10.1074/jbc.273.10.5419. View

13.

Galbiati F, Volonte D, Gil O, Zanazzi G, Salzer J, Sargiacomo M . Expression of caveolin-1 and -2 in differentiating PC12 cells and dorsal root ganglion neurons: caveolin-2 is up-regulated in response to cell injury. Proc Natl Acad Sci U S A. 1998; 95(17):10257-62. PMC: 21495. DOI: 10.1073/pnas.95.17.10257. View

14.

Lee H, Elmslie K . Gating of single N-type calcium channels recorded from bullfrog sympathetic neurons. J Gen Physiol. 1999; 113(1):111-24. PMC: 2222983. DOI: 10.1085/jgp.113.1.111. View

15.

Canti C, Page K, Stephens G, Dolphin A . Identification of residues in the N terminus of alpha1B critical for inhibition of the voltage-dependent calcium channel by Gbeta gamma. J Neurosci. 1999; 19(16):6855-64. PMC: 6782846. View

16.

Razani B, Rubin C, Lisanti M . Regulation of cAMP-mediated signal transduction via interaction of caveolins with the catalytic subunit of protein kinase A. J Biol Chem. 1999; 274(37):26353-60. DOI: 10.1074/jbc.274.37.26353. View

17.

Romanenko V, Fang Y, Byfield F, Travis A, Vandenberg C, Rothblat G . Cholesterol sensitivity and lipid raft targeting of Kir2.1 channels. Biophys J. 2004; 87(6):3850-61. PMC: 1304896. DOI: 10.1529/biophysj.104.043273. View

18.

Tillman T, Cascio M . Effects of membrane lipids on ion channel structure and function. Cell Biochem Biophys. 2003; 38(2):161-90. DOI: 10.1385/CBB:38:2:161. View

19.

Ottico E, Prinetti A, Prioni S, Giannotta C, Basso L, Chigorno V . Dynamics of membrane lipid domains in neuronal cells differentiated in culture. J Lipid Res. 2003; 44(11):2142-51. DOI: 10.1194/jlr.M300247-JLR200. View

20.

Martens J, OConnell K, Tamkun M . Targeting of ion channels to membrane microdomains: localization of KV channels to lipid rafts. Trends Pharmacol Sci. 2004; 25(1):16-21. DOI: 10.1016/j.tips.2003.11.007. View