Factors related to the low resting membrane potentials of diseased human atrial muscles

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).