Abstract:
:The cardiac muscarinic potassium channel (IK.ACh) is activated by a G protein upon receptor stimulation with acetylcholine. The G protein subunit responsible for activation (G alpha versus G beta gamma) has been disputed. We used G beta gamma inhibitors derived from the beta-adrenergic kinase 1 (beta ARK1) to assess the relative importance of G beta gamma in IK.ACh activation. In rabbit atrial myocytes, IK.ACh had a conductance of 49 +/- 6.2 pS. In inside-out patches, the mean open time was 1.60 +/- 0.57 ms, mean time constant (tau o) was 1.59 +/- 0.53 ms, and mean closed time was 3.02 +/- 1.35 ms (n = 38). beta ARK1 is a G beta gamma-sensitive enzyme that interacts with G beta gamma through a defined sequence near its carboxyl terminus. A 28-amino-acid peptide derived from the carboxyl terminus of beta ARK1 (peptide G) increased the closed time to 10.04 ms (P < .001) and decreased opening probability (NPo) by 71% (P < .001). Fusion proteins containing the entire carboxyl terminus of beta ARK1, glutathione S-transferase beta ARK1ct and hexahistidine beta ARK1ct, decreased NPo by 67% (P = .03) and 48% (P = .009), respectively. They also both significantly increased the closed time. None of the inhibitors affected mean open time or channel amplitude. A control peptide derived from a neighboring region of beta ARK1 had no significant effect on IK.ACh activity. These results provide further evidence for the role of G beta gamma in the activation of IK.ACh.
journal_name
Circ Resjournal_title
Circulation researchauthors
Nair LA,Inglese J,Stoffel R,Koch WJ,Lefkowitz RJ,Kwatra MM,Grant AOdoi
10.1161/01.res.76.5.832subject
Has Abstractpub_date
1995-05-01 00:00:00pages
832-8issue
5eissn
0009-7330issn
1524-4571journal_volume
76pub_type
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更新日期:1996-03-01 00:00:00
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更新日期:2002-09-06 00:00:00
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