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The Ionic Bases of the Action Potential in Isolated Mouse Cardiac Purkinje Cell #MMPMID23041576
Vaidyanathan R; O?Connell RP; Deo M; Milstein ML; Furspan P; Herron TJ; Pandit SV; Musa H; Berenfeld O; Jalife J; Anumonwo JM
Heart Rhythm 2013[Jan]; 10 (1): 80-7 PMID23041576show ga
Aims: Collecting electrophysiological and molecular data from the murine conduction system presents technical challenges. We have developed an approach for the isolation of murine Purkinje cells (PCs), characterized the major ionic currents and use the ionic data to simulate action potentials (APs) recorded from the isolated PCs. Methods and Results: 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 simulated a PC action potential, based on our experimental data. APs recorded from PCs were significantly longer than those recorded from ventricular cells. The prominent plateau phase of the PC AP was very negative (~?40mV). Spontaneous activity was observed only in PCs. The inward rectifier current, IK1, demonstrated no significant differences compared to ventricular myocytes (VMs). However, sodium current density was larger, and the voltage-gated potassium current (Ito) density was significantly less in PCs compared to myocytes. T-Type Ca2+ currents (ICa-T) were present in PCs but not VMs. Computer simulations suggest that ICa-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 Ito and the presence of the ICa-T are important determinants of the longer and relatively negative plateau phase of the APs.