Experimental Physiology

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

J. M.  OWEN a1, C. C.  QUINN a1, R.  LEACH a2, J. B. C.  FINDLAY a2 and M. R.  BOYETT a1
a1 Department of Physiology, University of Leeds, Leeds LS2 9JT, UK
a2 Department of Biochemistry & Molecular Biology, University of Leeds, Leeds LS2 9JT, UK


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, δ, of the site is significantly different for Kir2.1 and Kir3.1/Kir3.4 ([eqv] 0·38 and [eqv] 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+ (δ, [eqv] 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 [eqv] 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.

(Received July 16 1998)
(Accepted October 6 1998)