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This Article Full Text Full Text (PDF) All Versions of this Article: 93/3/347    most recent expphysiol.2007.040881v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Bocchi, L. Articles by Vassalle, M. Search for Related Content PubMed PubMed Citation Articles by Bocchi, L. Articles by Vassalle, M.

¹ Department of Physiology and Pharmacology, State University of New York, Downstate Medical Centre, 450 Clarkson Avenue, Brooklyn, NY 11203, USA

The aim of our experiments was to investigate by means of a whole cell patch-clamp technique the characteristics of the slowly inactivating sodium current (I_Na2) found in the plateau range in canine cardiac Purkinje single cells. The I_Na2 was separated from the fast-activating and -inactivating I_Na (labelled here I_Na1) by applying a two-step protocol. The first step, from a holding potential (V_h) of –90 or –80 mV to –50 mV, led to the quick activation and inactivation of I_Na1. The second step consisted of depolarizations of increasing amplitude from –50 mV to less negative values, which led to the quick activation and slow inactivation of I_Na2. The I_Na2 was fitted with a double exponential function with time constants of tens and hundreds milliseconds, respectively. After the activation and inactivation of I_Na1 at –50 mV, the slope conductance was very small and did not change with time. Instead, during I_Na2, the slope conductance was larger and decreased as a function of time. Progressively longer conditioning steps at –50 mV resulted in a progressive decrease in amplitude of I_Na2 during the subsequent test steps. Gradually longer hyperpolarizing steps (increments of 100 ms up to 600 ms) from V_h –30 mV to –100 mV were followed on return to –30 mV by a progressively larger I_Na2, as were gradually more negative 500 ms steps from V_h –30 mV to –90 mV. At the end of a ramp to –20 mV, a sudden repolarization to approximately –35 mV fully deactivated I_Na2. The I_Na2 was markedly reduced by lignocaine (lidocaine) and by low extracellular [Na⁺], but it was little affected by low and high extracellular [Ca²⁺]. At negative potentials, the results indicate that there was little overlap between I_Na2 and the transient outward current, I_to, as well as the calcium current, I_Ca. In the absence of I_to and I_Ca (blocked by means of 4-aminopyridine and nickel, respectively), I_Na2 reversed at 60 mV. In conclusion, I_Na2 is a sodium current that can be initiated after the inactivation of I_Na1 and has characteristics that are quite distinct from those of I_Na1. The results have a bearing on the mechanisms underlying the long plateau of Purkinje cell action potential and its modifications in different physiological and pathological conditions.

(Received 2 October 2007; accepted after revision 2 November 2007; first published online 9 November 2007)
Corresponding author M. Vassalle: Department of Physiology, Box 31, SUNY, Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203, USA. Email: mario.vassalle{at}downstate.edu