Reverse Na+/Ca2+-exchange mediated Ca2+-entry and noradrenaline release in Na+-loaded peripheral sympathetic nerves

Tamás L. Török, Dániel Rácz, Zsuzsanna Sáska, Ádám Z. Dávid, Tamás Tábi, Stefan Zillikens, Somaia A. Nada, Imre Klebovich, Klára Gyires, Kálmán Magyar

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

[3H]noradrenaline ([3H]NA) released from sympathetic nerves in the isolated main pulmonary artery of the rabbit was measured in response to field stimulation (2 Hz, 1 ms, 60 V for 3 min) in the presence of uptake blockers (cocaine, 3 × 10-5 M and corticosterone, 5 × 10-5 M). The [3H]NA-release was fully blocked by the combined application of the selective and irreversible 'N-type' voltage-sensitive Ca2+-channel (VSCC)-blocker ω-conotoxin (ω-CgTx) GVIA (10-8 M) and the 'non-selective' VSCC-blocker aminoglycoside antibiotic neomycin (3 × 10-3 M). Na+-loading (Na+-pump inhibition by K+-free perfusion) was required to elicit further NA-release after blockade of VSCCs (ω-CgTx GVIA + neomycin). In K+-free solution, in the absence of functioning VSCCs (ω-CgTx GVIA + neomycin), the fast Na+-channel activator veratridine (10-5 M) further potentiated the nerve-evoked release of [3H]NA. This NA-release was significantly inhibited by KB-R7943, and fully blocked by C ao2 + - removal. However, Li+-substitution was surprisingly ineffective. The non-selective K+-channel blocker 4-aminopyridine (4-AP, 10-4 M) also further potentiated the nerve-evoked release of NA in K+-free solution. This potentiated release was concentration-dependently inhibited by KB-R7943, significantly inhibited by Li+-substitution and abolished by C ao2 + - removal. It is concluded that in Na+-loaded sympathetic nerves, in which the VSCCs are blocked, the reverse Na+/Ca2+-exchange-mediated Ca2+-entry is responsible for transmitter release on nerve-stimulation. Theoretically we suppose that the fast Na+-channel and the exchanger proteins are close to the vesicle docking sites.

Original languageEnglish
Pages (from-to)338-345
Number of pages8
JournalNeurochemistry international
Volume53
Issue number6-8
DOIs
Publication statusPublished - Dec 1 2008

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Keywords

  • Delayed rectifier K-channel
  • Na-pump
  • Rabbit main pulmonary artery
  • Reverse Na/Ca-exchange
  • Voltage-sensitive Ca-channel
  • Voltage-sensitive Na-channel
  • [H]noradrenaline release

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

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