Effect of Extracellular Cations on the Inward Rectifying K⁺ Channels Kir2.1 and Kir3.1/Kir3.4

Abstract

The effects of Ba2+, Mg2+, Ca2+ and Na+ as blocking ions were investigated in 90 and 10 mM extracellular K+ solutions on the cloned inward rectifying K+ channel Kir2.1 expressed in Xenopus oocytes. Some data were also obtained using another inward rectifying K+ channel Kir3.1/Kir3.4. The addition of Ba2+ caused a concentration-, voltage- and time-dependent block of both channels. Decreasing the extracellular K+ concentration augmented the block. The data suggest that Ba2+ blocks the channels by binding to a site within the channel pore and that the electrical binding distance, delta, of the site is significantly different for Kir2.1 and Kir3. 1/Kir3.4 (0.38 and 0.22, respectively). Mg2+ and Ca2+ caused an instantaneous concentration- and voltage-dependent block of both channels. With Kir2.1, decreasing the K+ concentration augmented the block. The voltage dependence of the block was less than that of Ba2+ ([delta], 0.1), indicating a more superficial binding site for these ions within the channel pore. The affinity of the channels for Mg2+ and Ca2+ was 1000-fold lower than that for Ba2+. Addition of Na+ resulted in a concentration-, voltage- and time-dependent block of Kir2.1, similar to that observed with Ba2+. The competition between the blocking cations (for Kir2.1: Ba2+, Mg2+, Ca2+; for Kir3. 1/Kir3.4: Ba2+) and extracellular K+ suggests that the binding sites for the blocking cations may be sites to which K+ binds as part of the normal passage of K+ through the channels. It is possible that under normal physiological conditions naturally occurring extracellular cations may partly block the two inward rectifying K+ channels.

The membrane estrogen receptor ligand STX rapidly enhances GABAergic signaling in NPY/AgRP neurons: role in mediating the anorexigenic effects of 17β-estradiol

“…2D). BaCl 2 (500 M) abrogated the baclofen response (data not shown), which is consistent with the GABA B receptors activating GIRK channels (20,28,41). Single-cell RT-PCR on 40 neurons from four animals confirmed that 87.5 Ϯ 4.8 and 72.5 Ϯ 4.8% of NPY/AgRP neurons expressed GABA B -R1 and -R2, respectively (Fig.…”

G Protein-Activated (GIRK) Current in Rat Ventricular Myocytes is Masked by Constitutive Inward Rectifier Current (I_K1)

“…Figure 5 shows concentration-response curves for the inhibitory effect of Ba 2+ on ventricular I K1 and on atrial I K(ACh) . In line with a previous study, I K(ACh) was less sensitive to Ba 2+ than I K1 [29]. The EC 50 for I K1 was determined as 1.2x10 -6 M and as 2.6x10 on I K1 and I K(ACh) in a representative ventricular myocyte.…”

The Ca2+release-activated Ca2+current (ICRAC) mediates store-operated Ca2+entry in rat microglia

“…The rationale was that, under these culturing conditions, rat microglia have a prominent Kir, which is thought to be Kir2.1. 24,47 Both this Kir current and cloned Kir2.1 channels are blocked by external divalent cations; 24,47,58 thus, DVF solution might have reversed the channel block. Because Kir2.1 can be blocked by external Cs + , 59 we repeated the experiment from Figure 7A, but with 10 mM Cs + added to the DVF solution.…”