title: Subcellular heterogeneity of sodium current properties in adult cardiac ventricular myocytes.
abstract: BACKGROUND
  Sodium channel α-subunits in ventricular myocytes (VMs) segregate either to the intercalated disc or to lateral membranes, where they associate with region-specific molecules.
  
  
  OBJECTIVE
  To determine the functional properties of sodium channels as a function of their location in the cell.
  
  
  METHODS
  Local sodium currents were recorded from adult rodent VMs and Purkinje cells by using the cell-attached macropatch configuration. Electrodes were placed either in the cell midsection (M) or at the cell end (area originally occupied by the intercalated disc [ID]). Channels were identified as tetrodotoxin (TTX)-sensitive (TTX-S) or TTX-resistant (TTX-R) by application of 100 nM of TTX.
  
  
  RESULTS
  Average peak current amplitude was larger in ID than in M and largest at the site of contact between attached cells. TTX-S channels were found only in the M region of VMs and not in Purkinje myocytes. TTX-R channels were found in both M and ID regions, but their biophysical properties differed depending on recording location. Sodium current in rat VMs was upregulated by tumor necrosis factor-alpha. The magnitude of current increase was largest in the M region, but this difference was abolished by application of 100 nM of TTX.
  
  
  CONCLUSIONS
  Our data suggest that (a) a large fraction of TTX-R (likely Na(v)1.5) channels in the M region of VMs are inactivated at normal resting potential, leaving most of the burden of excitation to TTX-R channels in the ID region; (b) cell-cell adhesion increases functional channel density at the ID; and (c) TTX-S (likely non-Na(v)1.5) channels make a minimal contribution to sodium current under control conditions, but they represent a functional reserve that can be upregulated by exogenous factors.
authors.affiliation: Leon H. Charney Division of Cardiology, New York University School of Medicine, New York, New York 10016, USA.
authors.forename: Xianming
authors.initials: X
authors.lastname: Lin
authors.forename: Nian
authors.initials: N
authors.lastname: Liu
authors.forename: Jia
authors.initials: J
authors.lastname: Lu
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Justus M B
authors.initials: JM
authors.lastname: Anumonwo
authors.forename: Lori L
authors.initials: LL
authors.lastname: Isom
authors.forename: Glenn I
authors.initials: GI
authors.lastname: Fishman
authors.forename: Mario
authors.initials: M
authors.lastname: Delmar
mesh_terms: D000818:Animals; D002450:Cell Communication; D051379:Mice; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D026941:Sodium Channel Blockers; D015222:Sodium Channels; D014409:Tumor Necrosis Factor-alpha; D013779:Tetrodotoxin