title: Effects of elevating [Na]i on membrane currents of canine ventricular myocytes: role of intracellular Ca ions.
abstract: OBJECTIVE
  Our first objective was to study how elevating [Na]i can modify the background membrane conductance in canine ventricular myocytes (CVM). In particular, we wanted to find evidence for a Nai-activated K current (IK,Na) in these cells. The second objective was to compare the effects of elevating [Na]i on membrane currents without and with intracellular Ca buffering.
  
  
  METHODS
  Whole-cell currents were recorded and [Na]i was elevated either by using a pipette perfusion device that allowed [Na] in the pipette solution to be varied (from 0 to 50 mM), or by 50 microM ouabain.
  
  
  RESULTS
  Although an outward current attributable to IK,Na was confirmed in guinea-pig ventricular myocytes (GPVM) under our recording conditions, no such current was seen in 29 CVM examined. With Cai buffering, the main effect of elevating [Na]i on CVM was an increase in inward current around and negative to the resting membrane potential. Based on the dependence of this Nai-induced inward current on K ions and its pharmacological properties, especially the effects of low concentrations of external Ba ions (< or = 5 microM) at strongly hyperpolarized voltages, we hypothesize that this current was carried by extracellular K ions through the inward rectifier (IK1) channels that had been modified by the high level of [Na]i. With Cai buffering, elevating [Na]i by ouabain had few or no effects on the L-type Ca channel current (ICa) or the slow delayed rectifier current (IKs). Without Cai buffering, ouabain induced a rapid reduction of both currents along with an increase in a time-independent outward current at voltages positive to -60 mV.
  
  
  CONCLUSIONS
  Our data suggest that there are species variations in K channel expression and/or K channel modulation by intracellular Na ions. Furthermore, intracellular Ca ions play a crucial role in mediating the effects of Nai loading on membrane currents in canine ventricular myocytes.
authors.affiliation: Department of Pharmacology, Columbia University, New York, NY 10032, USA.
authors.forename: N C
authors.initials: NC
authors.lastname: Saxena
authors.forename: J S
authors.initials: JS
authors.lastname: Fan
authors.forename: G N
authors.initials: GN
authors.lastname: Tseng
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001464:Barium / Q000378:metabolism; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D003956:Dialysis; D004285:Dogs; D006168:Guinea Pigs; D007424:Intracellular Fluid / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism / Q000494:pharmacology*; D013045:Species Specificity
chemical_list: D000889:Anti-Arrhythmia Agents; D001464:Barium; D010042:Ouabain; D012964:Sodium; D011188:Potassium; D002118:Calcium