title: Factors related to the low resting membrane potentials of diseased human atrial muscles.
abstract: We studied the ionic mechanism of low resting potential (RP) of quiescent "diseased" human atrial fibers. The RP was -49.7 +/- 0.8 mV (n = 179) in normal Tyrode's solution (5.4 mM [K]o, 36 degrees C). The changes in RP measured at various levels of [K]o appeared to fit the RP-[K]o relationship predicted by the Goldman-Hodgkin-Katz equation, assuming PNa/PK ratio (alpha) to be 0.102 and [K]i to be 131.9 mM. The alpha far exceeded the normal value (about 0.01) by a factor of 10. Acetylcholine (ACh, 10 microM) led to marked increases in the RP. An application of tetrodotoxin (TTX, 6 microM) and perfusion with low [Na]o (10% of the control) media in the presence and absence of ACh produced considerable hyperpolarizations of the RP. These findings indicate that increased alpha value is due to a combination of decreased PK and increased PNa. Applications of ouabain (5 microM) and a cooling procedure (12.3 degrees C) depolarized the membrane, whereas epinephrine (1 microM) hyperpolarized it. Transient hyperpolarization, which exceeded the steady state levels of RP at 5.4 mM [K]o, was observed with perfusing of 5.4 mM [K]o media following perfusion with K-free media. These findings suggest that electrogenic Na pump current plays a significant role in the maintenance of the RP. In conclusion, partial depolarization of "diseased" human atrial fibers was attributed to both decreases in membrane K+ conductance and increases in Na+ conductance. The electrogenic outward pump current seemed to protect the fibers from severe depolarization produced by the conductance abnormality (increased PNa/PK).
mesh_terms: D000109:Acetylcholine / Q000502:physiology; D004573:Electrolytes / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology; D006325:Heart Atria / Q000503:physiopathology*; D006331:Heart Diseases / Q000503:physiopathology*; D006801:Humans; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D008564:Membrane Potentials; D010042:Ouabain / Q000494:pharmacology; D010477:Perfusion; D013696:Temperature; D013779:Tetrodotoxin / Q000493:pharmacokinetics
chemical_list: D004573:Electrolytes; D007473:Ion Channels; D013779:Tetrodotoxin; D010042:Ouabain; D000109:Acetylcholine; D004837:Epinephrine