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Inhibition of N‐type Calcium Channels: The Only Mechanism by which Presynaptic α 2 ‐Autoreceptors Control Sympathetic Transmitter Release
Author(s) -
Boehm Stefan,
Huck Sigismund
Publication year - 1996
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.1996.tb01336.x
Subject(s) - autoreceptor , mechanism (biology) , neuroscience , presynaptic inhibition , transmitter , voltage dependent calcium channel , calcium , chemistry , computer science , biology , physics , receptor , serotonin , telecommunications , channel (broadcasting) , excitatory postsynaptic potential , biochemistry , organic chemistry , quantum mechanics , inhibitory postsynaptic potential
α 2 ‐Adrenoceptors are known to inhibit voltage‐dependent Ca 2+ channels located at neuronal cell bodies; the present study investigated whether this or alternative mechanisms, possibly downstream of Ca 2+ entry, underlie the presynaptic α 2 ‐adrenergic modulation of transmitter release from chick sympathetic neurons. Using chick sympathetic neurons, overflow of previously incorporated [ 3 H]noradrenaline was elicited in the presence of extracellular Ca 2+ by electrical pulses, 25 mM K + or 10μM nicotine, or by adding Ca 2+ to otherwise Ca 2+ ‐free medium when cells had been made permeable by the calcium ionophore A23187 or by α‐latrotoxin. Pretreatment of neurons with the N‐type Ca 2+ channel blocker ω‐conotoxin GVIA and application of the α 2 ‐adrenergic agonist UK 14304 reduced the overflow elicited by electrical pulses, K + or nicotine, but not the overflow caused by Ca 2+ after permeabilization with α‐latrotoxin or A23187. In contrast, the L‐type Ca 2+ channel blocker nitrendipine reduced the overflow due to K + and nicotine, but not the overflow following electrical stimulation or α‐latrotoxin‐ and A23187‐permeabilization. The inhibition of electrically evoked overflow by UK 14304 persisted in the presence of nitrendipine and the L‐type Ca 2+ channel agonist BayK 8644, which per se enhanced overflow. In ω‐conotoxin GVIA‐treated cultures, electrically evoked overflow was also enhanced by BayK 8644 and almost reached the value obtained in untreated neurons. However, UK 14304 lost its effect under these conditions. Whole‐cell recordings of voltage‐activated Ca 2+ currents corroborated these results: UK 14304 inhibited Ca 2+ currents by 33%, nitrendipine caused a 7% reduction, and BayK 8644 increased the currents by 30%. Moreover, the dihydropyridines failed to abolish the inhibition by UK 14304, but pretreatment with ω‐conotoxin GVIA, which reduced mean amplitude from 0.95 to 0.23 nA, entirely prevented α 2 ‐adrenergic effects. Our results indicate that the α 2 ‐autoreceptor‐mediated modulation of noradrenaline release from chick sympathetic neurons relies exclusively on the inhibition of ω‐conotoxin GVIA‐sensitive N‐type Ca 2+ channels. Mechanisms downstream of these channels and voltage‐sensitive Ca 2+ channels other than N‐type appear not to be important.