Acetylcholine-sensitive muscarinic K+ channels in mammalian ventricular myocytes.
Acetylcholine (ACh) is known to increase K+ conductance in the atrium and in pacemaker tissues in the heart. This effect has not been well defined in mammalian ventricular tissues. We have identified and characterized the ACh-sensitive muscarinic K+ channel [IK(ACh)] activity in isolated human, cat, and guinea pig ventricular myocytes using the patch-clamp technique. Application of ACh increased whole cell membrane current in human ventricular myocytes. Current-voltage relationship of the ACh-induced current in ventricle exhibited inward-rectification whose slope conductance was smaller than that in atrium. In single-channel recording from cell-attached patches, IK(ACh) activity was observed when ACh was included in the solution. The channel exhibited a slope conductance of 43 +/- 2 pS. Open times were distributed according to a single exponential function with mean open lifetime of 1.8 +/- 0.3 ms. The channel had conductance and kinetic characteristics similar to human atrial IK(ACh), which had a slope conductance of 43 +/- 3 pS and mean open lifetime of 1.6 +/- 0.3 ms. However, concentration of ACh at half-maximal stimulation (KD) of the channel in ventricle was greater (KD = 0.13 microM) than that in atrium (KD = 0.03 microM). Adenosine caused activation of the same K+ channel. After formation of an excised inside-out patch, channel activity disappeared. Application of GTP (100 microM) or GTP gamma S (100 microM) to the solution caused reactivation of the channel. When myocytes were preincubated with pertussis toxin (PTX), ACh failed to activate these channels, indicating that the PTX-sensitive G protein, Gi, is essential for activation of IK(ACh). IK(ACh) channel activity was also found in cat and guinea pig ventricular myocytes. We conclude that ACh directly activates the IK(ACh) in mammalian ventricular myocytes via Gi in a fashion almost identical to atrial myocytes.
Koumi
S
S
Reingold ECG Center, Department of Medicine, Northwestern University School of Medicine, Chicago, Illinois 60611.
Wasserstrom
J A
JA
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D002415:Cats; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006325:Heart Atria; D006352:Heart Ventricles; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D009206:Myocardium / Q000166:cytology; D009928:Organ Specificity; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D013045:Species Specificity
D015221:Potassium Channels; D011976:Receptors, Muscarinic; D006160:Guanosine Triphosphate; D000109:Acetylcholine