Functional interaction of auxiliary subunits and synaptic proteins with CaV1.3 May impart hair cell Ca2+ current properties

Haitao Song, Liping Nie, Adrian Rodriguez-Contreras, Zu Hang Sheng, Ebenezer N. Yamoah

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

We assessed the functional determinants of the properties of L-type Ca2+ currents in hair cells by co-expressing the pore-forming Cav1.3α1 subunit with the auxiliary subunits β1A and/or α. Because Ca2+ channels in hair cells are poised to interact with synaptic proteins, we also co-expressed the Cav1.3α1 subunit with syntaxin, vesicle-associated membrane protein (VAMP), and synaptosome associated protein of 25 kDa (SNAP25). Expression of the Cav1.3α1 subunit in human embryonic kidney cells (HEK 293) produced a dihydropyridine (DHP)-sensitive Ca2+ current (peak current density - 2.0 ± 0.2 pA/pF; n = 11). Co-expression with β1A and α, subunits enhanced the magnitude of the current (peak current density: Cav1.3α1 + β1A = -4.3 ± 0.8 pA/pF, n = 10; Cav1.3α1 + β1A + α = -4.1 ± 0.6 pA/pF, n = 9) and produced a leftward shift of approximately 9 mV in the voltage-dependent activation of the currents. Furthermore, co-expression of Cav1.3α1 with syntaxin/ VAMP/SNAP resulted in at least a twofold increase in the peak current density (-4.7 ± 0.2 pA/pF; n = 11) and reduced the extent of inactivation of the Ca2+ currents. Botulinum toxin, an inhibitor of syntaxin, accelerated the inactivation profile of Ca2+ currents in hair cells. Immunocytochemical data also indicated that the Ca2+ channels and syntaxin are co-localized in hair cells, suggesting there is functional interaction of the Cav1.3α1 with auxiliary subunits and synaptic proteins, that may contribute to the distinct properties of the DHP-sensitive channels in hair cells.

Original languageEnglish (US)
Pages (from-to)1143-1149
Number of pages7
JournalJournal of Neurophysiology
Volume89
Issue number2
DOIs
StatePublished - Feb 1 2003

ASJC Scopus subject areas

  • Physiology
  • Neuroscience(all)

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