Two distinct pathways of muscarinic current responses in rabbit sino-atrial node myocytes

Pflugers Arch. 1998 Dec;437(1):164-7. doi: 10.1007/s004240050763.


Acetycholine (ACh) slows the heart rate by acting on sino-atrial node currents. Low ACh concentrations act on muscarinic receptors to inhibit the hyperpolarization-activated current (if) by a adenosine 3',5'-cyclic monophosphate (cAMP)-dependent cytoplasmic pathway. ACh also activates a muscarinic potassium conductance (iK,ACh) via a pertussis toxin-sensitive guanine nucleotide-binding protein (G-protein) that gates the channel directly. This pathway has been called membrane-delimited or "fast" because cytoplasmic components are not required and hence activation is relatively rapid. Such a pathway has also been proposed for the muscarinic inhibition of if. Here we show that, under steady-state current conditions, 0.1-1 microM ACh activates iK,ACh with a time constant of 1 s or less that is inversely proportional to ACh concentration, consistent with a fast, membrane-delimited pathway. ACh also causes a significantly slower inhibition of if which is not proportional to ACh binding. The changes in if are consistent with muscarinic effects mediated exclusively through the cAMP pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / administration & dosage
  • Acetylcholine / pharmacology*
  • Animals
  • Cyclic AMP / pharmacology
  • Dose-Response Relationship, Drug
  • Electric Conductivity
  • GTP-Binding Proteins / physiology
  • Ion Channel Gating
  • Kinetics
  • Pertussis Toxin
  • Potassium / metabolism
  • Rabbits
  • Receptors, Muscarinic / drug effects
  • Receptors, Muscarinic / physiology*
  • Virulence Factors, Bordetella / pharmacology


  • Receptors, Muscarinic
  • Virulence Factors, Bordetella
  • Cyclic AMP
  • Pertussis Toxin
  • GTP-Binding Proteins
  • Acetylcholine
  • Potassium