Abstract
[H-3]noradrenaline ([H-3]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 x 10(-5) M and corticosterone, 5 x 10(-5) M). The [H-3]NA-release was fully blocked by the combined application of the selective and irreversible 'N-type' voltage-sensitive Ca2+- channel (VSCC)-blocker omega-conotoxin (omega-CgTx) GVIA (10(-8) M) and the 'non-selective' VSCC-blocker aminoglycoside antibiotic neomycin (3 x 10(-3) M). Na+-loading (Na+-pump inhibition by K+-free perfusion) was required to elicit further NA-release after blockade of VSCCs (omega-CgTx GVIA + neomycin). In K+-free solution, in the absence of functioning VSCCs (omega-CgTx GVIA + neomycin), the fast Na+-channel activator veratridine (10(-5) M) further potentiated the nerve-evoked release of [H-3]NA. This NA-release was significantly inhibited by KB-R7943, and fully blocked by Ca-o(2 center dot) - 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 Ca-o(2 center dot) - removal.
It is Concluded that in Na+-loaded sympathetic nerves, in which the VSCCs are blocked, the reverse Na+/Ca+-exchange-mediated Ca2+-entry is responsible for transmitter release oil nerve-stimulation. Theoretically we Suppose that the fast Na+-channel and the exchanger proteins are close to the vesicle docking sites. (C) 2008 Elsevier Ltd. All rights reserved.