SEARCH

SEARCH BY CITATION

Keywords:

  • cation channel;
  • muscarinic receptor;
  • carbachol;
  • ileal smooth muscle;
  • mouse small intestine

Background and purpose:

There is little information about the excitatory cholinergic mechanisms of mouse small intestine although this model is important for gene knock-out studies.

Experimental approach:

Using patch-clamp techniques, voltage-dependent and pharmacological properties of carbachol- or intracellular GTPγS-activated cationic channels in mouse ileal myocytes were investigated.

Key results:

Three types of cation channels were identified in outside-out patches (17, 70 and 140 pS). The voltage-dependent behaviour of the 70 pS channel, which was also the most abundantly expressed channel (∼0.35 μ−2) was most consistent with the properties of the whole-cell muscarinic current (half-maximal activation at −72.3±9.3 mV, slope of −9.1±7.4 mV and mean open probability of 0.16±0.01 at −40 mV; at near maximal activation by 50 μM carbachol). Both channel conductance and open probability depended on the permeant cation in the order: Cs+ (70 pS) >Rb+ (66pS) >Na+ (47 pS) >Li+ (30 pS). External application of divalent cations, quinine, SK&F 96365 or La3+ strongly inhibited the whole-cell current. At the single channel level the nature of the inhibitory effects appeared to be very different. Either reduction of the open probability (quinine and to some extent SK&F 96365 and La3+) or of unitary current amplitude (Ca2+, Mg2+, SK&F 96365, La3+) was observed implying significant differences in the dissociation rates of the blockers.

Conclusions and implications:

The muscarinic cation current of murine small intestine is very similar to that in guinea-pig myocytes and murine genetic manipulation should yield important information about muscarinic receptor transduction mechanisms.

British Journal of Pharmacology (2006) 149, 179–187. doi:10.1038/sj.bjp.0706852