title: The ionic bases of the action potential in isolated mouse cardiac Purkinje cell.
abstract: BACKGROUND
  Collecting electrophysiological and molecular data from the murine conduction system presents technical challenges. Thus, only little advantage has been taken of numerous genetically engineered murine models to study excitation through the cardiac conduction system of the mouse.
  
  
  OBJECTIVE
  To develop an approach for isolating murine cardiac Purkinje cells (PCs), to characterize major ionic currents and to use the data to simulate action potentials (APs) recorded from PCs.
  
  
  METHODS
  Light microscopy was used to isolate and identify PCs from apical and septal cells. Current and voltage clamp techniques were used to record APs and whole cell currents. We then simulated a PC AP on the basis of our experimental data.
  
  
  RESULTS
  APs recorded from PCs were significantly longer than those recorded from ventricular cells. The prominent plateau phase of the PC AP was very negative (≈-40 mV). Spontaneous activity was observed only in PCs. The inward rectifier current demonstrated no significant differences compared to ventricular myocytes (VMs). However, sodium current density was larger, and the voltage-gated potassium current density was significantly less in PCs compared with myocytes. T-type Ca(2+) currents (I(Ca,T)) were present in PCs but not VMs. Computer simulations suggest that I(Ca,T) and cytosolic calcium diffusion significantly modulate AP profile recorded in PCs, as compared to VMs.
  
  
  CONCLUSIONS
  Our study provides the first comprehensive ionic profile of murine PCs. The data show unique features of PC ionic mechanisms that govern its excitation process. Experimental data and numerical modeling results suggest that a smaller voltage-gated potassium current and the presence of I(Ca,T) are important determinants of the longer and relatively negative plateau phase of the APs.
authors.affiliation: Department of Pharmacology, SUNY Upstate Medical University, Syracuse, New York, USA.
authors.forename: Ravi
authors.initials: R
authors.lastname: Vaidyanathan
authors.forename: Ryan P
authors.initials: RP
authors.lastname: O'Connell
authors.forename: Makarand
authors.initials: M
authors.lastname: Deo
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Milstein
authors.forename: Philip
authors.initials: P
authors.lastname: Furspan
authors.forename: Todd J
authors.initials: TJ
authors.lastname: Herron
authors.forename: Sandeep V
authors.initials: SV
authors.lastname: Pandit
authors.forename: Hassan
authors.initials: H
authors.lastname: Musa
authors.forename: Omer
authors.initials: O
authors.lastname: Berenfeld
authors.forename: José
authors.initials: J
authors.lastname: Jalife
authors.forename: Justus M B
authors.initials: JM
authors.lastname: Anumonwo
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D006352:Heart Ventricles / Q000166:cytology*; D051379:Mice; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000502:physiology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000378:metabolism / Q000502:physiology; D011689:Purkinje Cells / Q000378:metabolism / Q000502:physiology*; D012964:Sodium / Q000378:metabolism
chemical_list: D015221:Potassium Channels; D012964:Sodium; D002118:Calcium