title: Modulation of membrane potential by an acetylcholine-activated potassium current in trout atrial myocytes.
abstract: Application of the current-clamp technique in rainbow trout atrial myocytes has yielded resting membrane potentials that are incompatible with normal atrial function. To investigate this paradox, we recorded the whole membrane current (I(m)) and compared membrane potentials recorded in isolated cardiac myocytes and multicellular preparations. Atrial tissue and ventricular myocytes had stable resting potentials of -87 +/- 2 mV and -83.9 +/- 0.4 mV, respectively. In contrast, 50 out of 59 atrial myocytes had unstable depolarized membrane potentials that were sensitive to the holding current. We hypothesized that this is at least partly due to a small slope conductance of I(m) around the resting membrane potential in atrial myocytes. In accordance with this hypothesis, the slope conductance of I(m) was about sevenfold smaller in atrial than in ventricular myocytes. Interestingly, ACh increased I(m) at -120 mV from 4.3 pA/pF to 27 pA/pF with an EC(50) of 45 nM in atrial myocytes. Moreover, 3 nM ACh increased the slope conductance of I(m) fourfold, shifted its reversal potential from -78 +/- 3 to -84 +/- 3 mV, and stabilized the resting membrane potential at -92 +/- 4 mV. ACh also shortened the action potential in both atrial myocytes and tissue, and this effect was antagonized by atropine. When applied alone, atropine prolonged the action potential in atrial tissue but had no effect on membrane potential, action potential, or I(m) in isolated atrial myocytes. This suggests that ACh-mediated activation of an inwardly rectifying K(+) current can modulate the membrane potential in the trout atrial myocytes and stabilize the resting membrane potential.
authors.affiliation: Cardiology Department, Institut Català de Cienciès Cardiovasculars, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Cristina E
authors.initials: CE
authors.lastname: Molina
authors.forename: Hans
authors.initials: H
authors.lastname: Gesser
authors.forename: Anna
authors.initials: A
authors.lastname: Llach
authors.forename: Lluis
authors.initials: L
authors.lastname: Tort
authors.forename: Leif
authors.initials: L
authors.lastname: Hove-Madsen
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002469:Cell Separation; D006325:Heart Atria / Q000166:cytology / Q000187:drug effects; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D018727:Muscarinic Antagonists / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D017686:Oncorhynchus mykiss / Q000502:physiology*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects*; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects / Q000502:physiology; D016276:Ventricular Function
chemical_list: D018727:Muscarinic Antagonists; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D001285:Atropine; D000109:Acetylcholine