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

Abstract.

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 _m, membrane currents and intracellular Ca²⁺ ([Ca²⁺]_i) 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 (≥1.2 mM). Effects of [Mg²⁺]_i on caffeine-induced currents were investigated. [Mg²⁺]_i selectively facilitated the activation of Ca²⁺-activated K⁺ currents (I _K,Ca), while Ca²⁺-activated Cl^– currents (I _Cl,Ca) were unaffected. Simultaneous recording of [Ca²⁺]_i and I _K,Ca at different [Mg²⁺]_i showed that [Mg²⁺]_i increased the Ca²⁺ sensitivity of I _K,Ca. [Ca²⁺]_i also inhibited voltage-dependent K⁺ (K_V) currents, although this effect was significant only at low [Mg²⁺]_i. These results imply that the relative contributions of I _K,Ca, I _Cl,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,Ca and inhibition of K_V currents depolarized V _m; at high [Mg²⁺]_i the activation of I _K,Ca predominated, resulting in hyperpolarization of V _m. In conclusion, [Mg²⁺]_i hyperpolarizes V _m by selective facilitation of I _K,Ca and may thus possibly contributes to the relaxation of the coronary artery.