Block of mouse Slo1 and Slo3 K+ channels by CTX, IbTX, TEA, 4-AP and quinidine

Qiong Yao Tang, Zhe Zhang, O. Ming Xia, Christopher J. Lingle

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

pH-regulated Slo3 channels, perhaps exclusively expressed in mammalian sperm, may play a role in alkalization-mediated K+ fluxes associated with sperm capacitation. The Slo3 channel shares extensive homology with Ca 2+- and voltage-regulated BK-type Slo1 K+ channels. Here, using heterologous expression in oocytes, we define distinctive differences in pharmacological properties of Slo3 and Slo1 currents, examine blockade in terms of distinct blocking models, and, for some blockers, use mutated constructs to evaluate determinants of block. Slo3 is resistant to block by the standard Slo1 blockers, iberiotoxin, charybdotoxin and extracellular TEA. Slo3 is relatively insensitive to extracellular 4-AP up to 100 mM, while Slo1 is blocked in a voltage-dependent fashion consistent with block on the extracellular side of the channel. Block of both Slo1 and Slo3 by cytosolic 4-AP can be described by open channel block, with Slo3 being ∼10-15-fold more sensitive, but exhibiting weaker voltage-dependence of block. The cytosolic concentrations of 4-AP required to block Slo3 make it unlikely that the effects of 4-AP on volume regulation in mammalian sperm is mediated by Slo3. Quinidine was more effective in blocking Slo3 than Slo1. For Slo1, quinidine block was favored by depolarization, irrespective of the side of application. For Slo3, quinidine block was relieved by depolarization, irrespective of the side of application, with strong block by less than 10 μM quinidine at potentials near 0 mV. The unusual voltage-dependence of block of Slo3 by quinidine may result from preferential binding of quinidine to closed Slo3 channels. The quinidine concentrations effective in blocking Slo3 suggest, that in experiments that have examined quinidine effects on sperm, any Slo3 currents would be almost completely inhibited.

Original languageEnglish
Pages (from-to)1-20
Number of pages20
JournalChannels
Volume4
Issue number1
DOIs
StatePublished - Jan 1 2010

Keywords

  • 4-aminopyridine
  • Channel block
  • KSper
  • Quinidine
  • Slo channels
  • Slo1
  • Slo3
  • α-KTX toxins

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