| 11682450 |
Ghisdal P, Morel N: Cellular target of voltage and calcium-dependent K (+) channel blockers involved in EDHF-mediated responses in rat superior mesenteric artery. Br J Pharmacol. 2001 Nov;134(5):1021-8.
1. We have investigated the cellular target of K (+) channel blockers responsible for the inhibition of the EDHF-mediated relaxation in the rat mesenteric artery by studying their effects on tension, smooth muscle cell (SMC) membrane potential and endothelial cell Ca (2+) signal ([Ca (2+)](endo)). 2. In arteries contracted with prostaglandin F (2 alpha) (2.5 - 10 microM), relaxation evoked by ACh (0.01 - 3 microM) was abolished by a combination of charybdotoxin (ChTX, 0.1 microM) plus apamin (Apa, 0.1 microM) and was inhibited by 68+/-6% (n=6) by 4-aminopyridine (4-AP, 5 mM). 3. ACh (0.001 - 3 microM) increased [Ca (2+)](endo) and hyperpolarized SMCs with the same potency, the pD (2) values were equal to 7.2+/-0.08 (n=4) and 7.2+/-0.07 (n=9), respectively. SMCs hyperpolarization to ACh (1 microM) was abolished by high K (+) solution or by ChTX/Apa. It was decreased by 66+/-5% (n=6) by 4-AP. 4. The increase in [Ca (2+)](endo) evoked by ACh (1 microM) was insensitive to ChTX/Apa but was depressed by 58+/-16% (n=6) and 27+/-4% (n=7) by raising external K (+) concentration and by 4-AP, respectively. 5. The effect of 4-AP on [Ca (2+)](endo) was not affected by increasing external K (+) concentration. In Ca-free/EGTA solution, the transient increase in [Ca (2+)](endo) evoked by ACh (1 microM) was abolished by thapsigargin (1 microM) and was decreased by 75+/-7% (n=5) by 4-AP. 6. These results show that inhibition of EDHF-evoked responses by 4-AP may be attributed to a decrease in the Ca (2+) release activated by ACh in endothelial cells. The abolition of SMCs hyperpolarization to ACh by ChTX/Apa is not related to an interaction with the [Ca (2+)](endo). |
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