Intracellular Mg2+ hyperpolarizes rabbit coronary artery smooth muscle cells by differential modulation of Ca2+i-dependent ion channels

We investigated the role of intracellular Mg2+ ([Mg2+](i)) in the regulation of membrane potential (V-m) in rabbit coronary artery smooth muscle cells. V membrane currents and intracellular Ca2+ ([Ca2+];) were measured using standard patch-clamp and microfluorometry techniques. When [Ca2+](i) was increased by caffeine, V-m depolarized at low [Mg2+](i) (0.1 mM), but hyperpolarized at high [Mg2+](i) (greater than or equal to1.2 mM). Effects of [Mg2+](i) on caffeine-induced currents were investigated. [Mg2+](i) selectively facilitated the activation of Ca2+-activated K+ currents (I-KCa), while Ca2+-activated Cl- currents (I-Cl,I-Ca) were unaffected. Simultaneous recording of [Ca2+](i) and I-K,I-Ca at different [Mg-i(2+]) showed that [Mg-i(2+]) increased the Ca2+ sensitivity of I-K,I-Ca. [Ca2+](i) also inhibited voltage-dependent K+ (Kv) currents, although this effect was significant only at low [Mg2+](i). These results imply that the relative contributions of I-K,I-Ca, I-Cl,I-Ca and K-V currents to V-m, during an increase in [Ca2+](i) are affected by [Mg2+](i): at low [Mg2+](i), activation of I-Cl,I-Ca and inhibition of Kv currents depolarized V-m,; at high [Mg2+](i) the activation of I-K,I-Ca predominated, resulting in hyperpolarization of V-m. In conclusion, [Mg2+](i) hyperpolarizes V-m by selective facilitation of I-K,I-Ca and may thus possibly contributes to the relaxation of the coronary artery.