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Am J Physiol Heart Circ Physiol 280: H2554-H2562, 2001;
0363-6135/01 $5.00
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Vol. 280, Issue 6, H2554-H2562, June 2001

Evidence of involvement of GIRK1/GIRK4 in long-term desensitization of cardiac muscarinic K+ channels

Zhigang Shui, Tomoko Takahashi Yamanushi, and Mark R. Boyett

School of Biomedical Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom

The cardiac M2 muscarinic receptor/G protein/K+ channel system was studied in neonatal rat atrial cells cultured with and without 10 µM carbachol (CCh) for 24 h. Channel activity in CCh-pretreated cells was substantially reduced as a result of long-term desensitization regardless of whether the channel was activated by ACh in cell-attached patches or GTP in inside-out patches. Channel activity in CCh-pretreated cells was also low when the receptor was bypassed and the G protein and channel were directly activated by [gamma -S]GTP or both the receptor and G protein were bypassed and the channel was directly activated by trypsin. Finally, in CCh-pretreated cells, the whole cell K+ current was low when the channel was activated via the independent adenosine receptor. This suggests that the channel is involved in long-term desensitization. However, in CCh-pretreated cells, although the receptor was internalized, there was no internalization of the channel. We suggest that the function of the muscarinic K+ channel declines in long-term desensitization of the cardiac M2 muscarinic receptor/G protein/K+ channel system.

heart; acetylcholine; muscarinic receptor


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