title: Hyperpolarization induced by sodium removal in rabbit sinoatrial node cells. Possible role of electrogenic sodium-calcium exchange.
abstract: Spontaneously active rabbit sinoatrial node (SAN) cells were bathed in K-free solution or in K-free ouabain (20 microM)-containing solution to depress the electrogenic Na(+)-K+ pump activity. In SAN cells exposed to K-free solution, the automatic action potentials ceased with gradual depolarization, followed by an eventual steady-state membrane potential of -32 +/- 1 mV. Under conditions where the Na(+)-K+ pump was blocked, removal of external Na+ produced a large and rapid hyperpolarization in the membrane potential and the membrane was hyperpolarized by 23 +/- 0.5 mV. When the external Na+ was lowered, Na+ was replaced by Li+. The Na-free hyperpolarization was not affected by applications of verapamil (4 microM), lidocaine (1 mM), and quinidine (50 microM), but was inhibited by either quinacrine (50 microM) or Cd2+ (10 mM), which are blockers of Na(+)-Ca2+ exchange. In the absence of external K+, replacement of external NaCl by sucrose produced a hyperpolarization similar to that seen in the replacement of external Na+ by Li+. In the K-free ouabain (20 microM)-containing solution, removal of external Na+ also produced a hyperpolarization, and the membrane potential dropped from -29 +/- 1 to -48 +/- 1 mV. The intracellular acidification due to NH4Cl removal after exposure to NH4Cl (20 mM) produced a decrease in Na-free hyperpolarization, which in the presence of ouabain was inhibited by the application of Cd2+ (10 mM). Removal of external Ca2+ nearly completely blocked Na-free hyperpolarization. It can be concluded that Na-free hyperpolarizations are related to the functioning of an electrogenic Na(+)-Ca2+ exchange mechanism.
authors.affiliation: Department of Physiology, Kanazawa Medical University, Uchinada, Ishikawa, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Miyamae
authors.forename: S
authors.initials: S
authors.lastname: Imanishi
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D066298:In Vitro Techniques; D008012:Lidocaine / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D010042:Ouabain / Q000494:pharmacology; D011796:Quinacrine / Q000494:pharmacology; D011802:Quinidine / Q000494:pharmacology; D011817:Rabbits; D012849:Sinoatrial Node / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects / Q000378:metabolism*; D014700:Verapamil / Q000494:pharmacology
chemical_list: D010042:Ouabain; D008012:Lidocaine; D012964:Sodium; D014700:Verapamil; D000254:Sodium-Potassium-Exchanging ATPase; D011796:Quinacrine; D011802:Quinidine; D002118:Calcium