Presynaptic α2-receptors regulate reverse Na +/Ca2+-exchange and transmitter release in Na +-loaded peripheral sympathetic nerves

Tamás L. Török, Zsolt Nagykáldi, Zsuzsanna Sáska, Timur Kovács, Somaia A. Nada, Stefan Zilliikens, Kálmán Magyar, E. Sylvester Vizi

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8 Citations (Scopus)


Electrical depolarisation-(2 Hz, 1 ms)-induced [3H]noradrenaline ([3H]NA) release has been measured from the isolated main pulmonary artery of the rabbit in the presence of uptake blockers (cocaine, 3×10-5 M; corticosterone, 5×10-5 M). Substitution of most of the external Na+ by Li+ (113 mM; [Na+]0: 25 mM) slightly potentiated the axonal stimulation-evoked release of [3H]NA in a tetrodotoxin (TTX, 10 -7 M) sensitive manner. The reverse Na+/Ca 2+-exchange inhibitor KB-R7943 (3×10-5 M) failed to inhibit the stimulation-evoked release of [3H]NA, but increased the resting outflow of neurotransmitter. The 'N-type' voltage-sensitive Ca 2+-channel (VSCC) blocker ω-conotoxin (ω-CgTx) GVIA (10-8 M) significantly and irreversibly inhibited the release of [3H]NA on stimulation (∼60-70%). The 'residual release' of NA was abolished either by TTX or by reducing external Ca2+ from 2.5 to 0.25 mM. The 'residual release' of NA was also blocked by the non-selective VSCC-blocker neomycin (3×10-3 M). Correlation was obtained between the extent of VSCC-inhibition and the transmitter release-enhancing effect of presynaptic α2-receptor blocker yohimbine (3×10-7 M). When the release of [3H]NA was blocked by ω-CgTx GVIA plus neomycin, yohimbine was ineffective. Inhibition of the Na+-pump by removal of K+ from the external medium increased both the resting and the axonal stimulation-evoked release of [ 3H]NA in the absence of functioning VSCCs (i.e., in the presence of neomycin and after ω-CgTx treatment). Under these conditions the stimulation-evoked release of NA was abolished either by TTX or by external Ca2+-removal (+1 mM EGTA). Similarly, external Li+ (113 mM) or the reverse Na+/Ca2+ exchange blocker KB-R7943 (3×10-5 M) significantly inhibited the stimulation-induced transmitter release in 'K+-free' solution. KB-R7943 decreased the resting outflow of NA as well. Under conditions in which the Na+-pump was inhibited in the absence of functioning VSCCs, yohimbine (3×10 -7 M) further enhanced the release of neurotransmitter, while l-noradrenaline (l-NA, 10-6 M), an agonist of presynaptic α2-receptors, inhibited it. The yohimbine-induced enhancement of NA-release was abolished by Li+-substitution and significantly inhibited by KB-R7943 application. It is concluded that after blockade of VSCCs brief depolarising pulses may reverse Na+/Ca2+-exchange and release neurotransmitter in Na+-loaded sympathetic nerves. Further, similar to that of VSCCs, the reverse Na+/Ca 2+-exchange may also be regulated by presynaptic α2- receptors.

Original languageEnglish
Pages (from-to)699-711
Number of pages13
JournalNeurochemistry international
Issue number5
Publication statusPublished - Oct 1 2004


  • Rabbit pulmonary artery
  • Reverse Na/Ca-exchange
  • [H]noradrenaline release
  • α-Receptor modulation

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

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