Elektrogén Na+/Ca2+-csere α2-receptor reguláciÓja perifériás szimpatikus idegen

Electrical depolarisation-(2 Hz, 1 ms)-induced [ 3 H]noradren-aline ([ 3 H]NA) release was measured from the isolated main pulmonary artery of the rabbit in the presence of uptake blockers (cocaine, 3x10 - 5 M; corticosterone, 5x10 - 5 M) and after blocking the MAO-enzyme by pargyline (1,2x10 - 4 M). Substitution of most of the external Na + by Li + (113 mM; [Na + ] o : 25 mM) slightly potentiated the stimulation-induced release of [ 3 H]NA in a tetrodotoxin (TTX, 10 - 7 M) sensitive manner. The reverse Na + /Ca 2 + -exchange inhibitor KB-R7943 (3x10 - 5 M) failed to inhibit the stimulation-evoked release of [ 3 H]NA, but increased the resting outflow of neurotransmitter. The 'N-type' voltage-sensitive Ca 2 + -channel (VSCC) blocker w-conotoxin (ω-CgTx) GVIA (10 - 8 M) significantly and irreversibly inhibited the release of [ 3 H]NA on stimulation (∼60-70%). The 'residual release' of NA was abolished either by TTX or by reducing external Ca 2 + from 2,5 to 0,25 mM. The 'residual release'of NA was also blocked by the non-selective VSCC-blocker neomycin (3x10 - 3 M). Direct correlation was obtained between the extent of VSCC-inhibition and the transmitter release enhancing-effect of presynaptic α 2 -receptor blocker yohimbine (3x10 - 7 M). When the release of [ 3 H]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 stimulation-evoked release of [ 3 H]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 Ca 2 + -removal (+1 mM EGTA). Similarly, external Li + (113 mM) or the reverse Na + /Ca 2 + exchange blocker KB-R7943 (3x10 - 5 M) significantly inhibited the nerve-evoked release of NA in 'K + -free' solution. KB-R7943 decreased the resting outflow of NA as we'l. Under conditions, in which the Na + -pump was inhibited in the absence of functioning VSCCs, yohimbine (3x10 - 7 M) further enhanced the release of neurotransmitter, while l-noradrenaline (l-NA, 10 - 6 M), an agonist of presynaptic α 2 -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+/Ca 2 + -exchange and release neurotransmitter in Na + -loaded sympathetic nerves. Further, similar to that of VSCCs, the reverse Na + /Ca 2 + -exchange may also be inhibited by presynaptic α 2 -receptor activation.