Fast and slow blockades of the inward-rectifier K+ channel by external divalent cations in guinea-pig cardiac myocytes

Abstract

The present patch-clamp study shows that external Mg2+, Ca2+ and Sr2+ decrease the unit amplitude of inward current through the inward-rectifier K+ channel in a concentration-dependent manner. Sr2+ produces a voltage-dependent flickering block as well, and the fractional electrical distance between the external orifice and the Sr2+ binding site (delta) is 0.73. The decrease of unit amplitude is reversible and voltage independent while it does not increase the noise level on the open-channel current. Unit current decreased by Mg2+ or Ca2+ has a longer mean open time, which is inversely proportional to the unit amplitude. External Mg2+ does not decrease the amplitude of unit outward current. A surface potential shift, measured using voltage-dependent Cs+ block (delta = 1.60), failed to explain the current decrease. Therefore, we conclude that (1) the external divalent cations cause an extremely fast channel block, which appears as a decreased amplitude of the unit current on the recording system; (2) the blocking site (fast site) is present near the external orifice of the channel, and it is separate from the blocking site (slow site) to which Cs+ and Sr2+ bind.

The tetravalent organic cation spermine causes the gating of the IRK1 channel expressed in murine fibroblast cells.

“…9) (Shioya, Matsuda & Noma, 1993), it is difficult to produce the shift of the time constant. Therefore, we speculate that the shift of the time constant was caused by the decrease in the transmembrane potential through screening the fixed negative charges on the membrane surface or at the channel orifice.…”

Effect of extracellular cations on the inward rectifying K+ channels Kir2.1 and Kir3.1/Kir3.4

“…The voltage dependence has led to the suggestion that the ions block the channel by binding to a site within the channel pore. In guinea-pig ventricular cells, Biermans et al (1987) and Shioya et al (1993) showed that extracellular cations normally present in the extracellular fluid (Mg¥ and Ca¥) block the inward rectifying K¤ current IK1. During hyperpolarizing pulses, Kir2.1 current shows a time-dependent inactivation and Kubo et al (1993a) suggested that this is due to channel block by cations present in normal extracellular fluid.…”

Does lindane (gamma-hexachlorocyclohexane) increase the rapid delayed rectifier outward K+ current (I Kr) in frog atrial myocytes?

“…The lindane-increased I out cannot be attributed to the opening of lindane-induced ionic channels since lindane has been shown to be devoid of ionophoretic properties in planar lipid bilayers [9]. Our data show that the lindane-increased I out still persists in the presence of Sr 2+ which is known to block the background I K1 [12] and I K-Ca [13] currents in cardiac tissues. Our findings reveal that quinidine inhibits the effect of lindane on I out .…”