Effects of intracellular magnesium on Kv1.5 and Kv2.1 potassium channels

Abstract

We characterized the effects of intracellular Mg(2+) (Mg(2+) (i)) on potassium currents mediated by the Kv1.5 and Kv2.1 channels expressed in Xenopus oocytes. Increase in Mg(2+) (i) caused a voltage-dependent block of the current amplitude, apparent acceleration of the current kinetics (explained by a corresponding shift in the steady-state activation) and leftward shifts in activation and inactivation dependencies for both channels. The voltage-dependent block was more potent for Kv2.1 [dissociation constant at 0 mV, K(d)(0), was approximately 70 mM and the electric distance of the Mg(2+) binding site, delta, was 0.2] than for the Kv1.5 channel [K(d)(0) approximately 40 mM and delta = 0.1]. Similar shifts in the voltage-dependent parameters for both channels were described by the Gouy-Chapman formalism with the negative charge density of 1 e(-)/100 A(2). Additionally, Mg(2+) (i) selectively reduced a non-inactivating current and increased the accumulation of inactivation of the Kv1.5, but not the Kv2.1 channel. A potential functional role of the differential effects of Mg(2+) (i) on the Kv channels is discussed.

Hypoxic Pulmonary Vasoconstriction

“…These results suggest that K V channel inhibition was secondary to an hypoxia-induced rise in[Ca 2ϩ ] and would therefore be more likely to amplify than to initiate hypoxic depolarization. In line with this possibility, agents that release Ca 2ϩ from sarcoplasmic reticulum increased both [Ca 2ϩ ] i and E m in isolated PASMC, and abolished these responses to subsequent hypoxic exposures(598).High levels of [Mg 2ϩ ] i attenuated currents conducted by several K V channel subtypes, including K V 1.5 and K V 2.1(1888), and inhibited I KV in several types of smooth muscle cells, including PASMC(599). In rat PASMC, increased [Mg 2ϩ ] i caused I KV to activate at more negative E m and decrease in amplitude, similar to the effects of the mitochondrial inhibitors antimycin A and CCCP, both of which also increased [Mg 2ϩ ] i (527).…”

Putative pore‐loops of TMEM16/anoctamin channels affect channel density in cell membranes

“…Normalised G ( G / G max ) was plotted against the voltage of the pre‐pulse. Under these conditions, the amplitude of the G / G max is directly proportional to the open probability ( P o ) of the channel at the pre‐pulse voltage (Bezanilla, 2000; Tammaro et al 2005). The constructed relationships were fitted with the Boltzmann equation of the form: where z is the number of gating charges moving through the entire applied field during channel activation, V 0.5 is the voltage at which the G is half‐maximal and is associated with the conformational energy required for the channel to open, F is Faraday's constant, R is the universal gas constant and T is the absolute temperature.…”

Modulation of the voltage-dependent K current by intracellular Mg in rat aortic smooth muscle cells

“…Qualitatively similar suppression of K V currents was demonstrated in canine and rabbit arterial SMCs [12]. Although the mechanism of inhibition has not been clarified in these reports, it was apparently different to the voltage-dependent block of heterologously expressed K V channels by Mg 2+ i that occurs at positive membrane potentials (N+40 mV) [13][14][15][16].…”

“…Although the mechanism of this effect remains to be clarified, it is likely to be mediated by a Mg 2+ i -dependent process. The inward rectification of I Kv in high Mg 2+ i closely mimics the voltage-dependent block of cloned K V channels [13][14][15][16] and could share a similar mechanism. However, occurring at very positive voltages, this effect is unlikely to have a great impact on vascular contractility.…”

“…However, occurring at very positive voltages, this effect is unlikely to have a great impact on vascular contractility. It is noteworthy that increased Mg 2+ i caused a similar type of rectification of the cloned Kv2.1 channel [16], which was proposed to be a molecular correlate of the I Kv in RAMs [18].…”