Electrical field stimulation (EFS)-induced relaxations turn into contractions upon removal of extracellular calcium in rat mesenteric artery

In the present study, we aimed to examine the effect of blockade of L-type Ca2+ channels (LTCC) and in addition the removal of extracellular Ca2+, on EFS-induced relaxations in rings of rat mesenteric artery. EFS applied to the tissues precontracted with phenylephrine caused relaxations which were markedly inhibited by nifedipine (10−7 M) and tetraethylammonium (TEA) (1 mM). Addition of LTCC opener BAY K 8644 (10−7 M) failed to enhance the relaxations. Upon removal of Ca2+, EFS with the same stimulation parameters produced frequency-dependent transient contractions. Tetrodotoxin (10−6 M), capsaicin (10−5 M) and removal of endothelium did not alter these contractions suggesting that they were not neural in origin and endothelium-derived contracting factors were unlikely to be involved. However, they were increased by nearly 40% in response to BAY K 8644 (10−7 M) and were inhibited by nifedipine (10−7 M), indicating that activation of the LTCCs was essential. Inositol triphosphate (InsP3) receptor antagonist 2-APB (10−4 M) significantly reduced, and high concentration of caffeine (20 mM) almost totally suppressed the contractions. These results suggest that in the absence of extracellular Ca2+ EFS through membrane depolarization, evokes the opening of the LTCCs which subsequently leads to the release of Ca2+ from internal stores via InsP3 receptors, a phenomenon known as Ca2+ channel-induced Ca2+ release (CCICR), to trigger vasoconstriction. That activation of LTCCs causes arterial relaxation or contraction depending on the Ca2+ status apparently exemplifies how the same messenger fulfils opposing physiological functions in a given cell.

(A) EFS-induced relaxations in normal Krebs–Henseleit solution turn into contractions upon removal of Ca2+ in rat mesenteric arterial rings precontracted with phenylephrine. (B) Effects of BAY K8644, nifedipine, caffeine and 2-APB on EFS-induced contractions upon removal of Ca2+ in rat mesenteric arterial ringsFigure optionsDownload high-quality image (80 K)Download as PowerPoint slide