Complex rectification of Müller cell Kir currents

Yuriy V. Kucheryavykh, Yaroslav M. Shuba, Sergei M. Antonov, Mikhail Y. Inyushin, Luis Cubano, Wade L. Pearson, Harley Kurata, Andreas Reichenbach, Rüdiger W. Veh, Colin G. Nichols, Misty J. Eaton, Serguei N. Skatchkov

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Although Kir4.1 channels are the major inwardly rectifying channels in glial cells and are widely accepted to support K+- and glutamate-uptake in the nervous system, the properties of Kir4.1 channels during vital changes of K+ and polyamines remain poorly understood. Therefore, the present study examined the voltage-dependence of K+ conductance with varying physiological and pathophysiological external [K+] and intrapipette spermine ([SP]) concentrations in Müller glial cells and in tsA201 cells expressing recombinant Kir4.1 channels. Two different types of [SP] block were characterized: "fast" and "slow." Fast block was steeply voltage-dependent, with only a low sensitivity to spermine and strong dependence on extracellular potassium concentration, [K+]o. Slow block had a strong voltage sensitivity that begins closer to resting membrane potential and was essentially [K+]o-independent, but with a higher spermine- and [K+]i-sensitivity. Using a modified Woodhull model and fitting i/V curves from whole cell recordings, we have calculated free [SP]in in Müller glial cells as 0.81 ± 0.24 mM. This is much higher than has been estimated previously in neurons. Biphasic block properties underlie a significantly varying extent of rectification with [K+] and [SP]. While confirming similar properties of glial Kir and recombinant Kir4.1, the results also suggest mechanisms underlying K+ buffering in glial cells: When [K+]o is rapidly increased, as would occur during neuronal excitation, "fast block" would be relieved, promoting potassium influx to glial cells. Increase in [K+]in would then lead to relief of "slow block," further promoting K+-influx.

Original languageEnglish
Pages (from-to)775-790
Number of pages16
JournalGlia
Volume56
Issue number7
DOIs
StatePublished - May 2008

Keywords

  • Glia
  • Kir4.1
  • Polyamine
  • Spermine
  • Voltage-dependence

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