title: Electrical field stimulation (EFS)-induced relaxations turn into contractions upon removal of extracellular calcium in rat mesenteric artery.
abstract: In the present study, we aimed to examine the effect of blockade of L-type Ca(2+) channels (LTCC) and in addition the removal of extracellular Ca(2+), 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) (1mM). Addition of LTCC opener BAY K 8644 (10(-7)M) failed to enhance the relaxations. Upon removal of Ca(2+), 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 (20mM) almost totally suppressed the contractions. These results suggest that in the absence of extracellular Ca(2+) EFS through membrane depolarization, evokes the opening of the LTCCs which subsequently leads to the release of Ca(2+) from internal stores via InsP3 receptors, a phenomenon known as Ca(2+) channel-induced Ca(2+) release (CCICR), to trigger vasoconstriction. That activation of LTCCs causes arterial relaxation or contraction depending on the Ca(2+) status apparently exemplifies how the same messenger fulfils opposing physiological functions in a given cell.
authors: Department of Pharmacology, Faculty of Pharmacy, Hacettepe University, 06100 Sihhiye, Ankara, Turkey.
authors: Melike Hacer
authors: MH
authors: Ozkan
authors: Elif Inci
authors: EI
authors: Ozturk
authors: Serdar
authors: S
authors: Uma
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D004558:Electric Stimulation; D005110:Extracellular Space / Q000378:metabolism*; D008297:Male; D017538:Mesenteric Artery, Superior / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D014662:Vasoconstrictor Agents; D002118:Calcium