Optical measurements of transmembrane potential changes during electric field stimulation of ventricular cells

Academic Article

Abstract

  • We evaluated transmembrane potential changes at the ends of isolated rabbit ventricular myocytes during defibrillation-strength shocks given in the cellular refractory period. The myocytes were stimulated (S1 pulse) to produce an action potential. Then a constant-field shock (S2 pulse) with an electric field of 20 or 40 V/cm was given at an S1-S2 interval of 50 msec. The cells were stained with potentiometric dye (di-4-ANEPPS), and the cell end facing the S2 anode or cathode was illuminated with a laser while the fluorescence was recorded. During S2, the cell end facing the S2 cathode became more positive intracellularly, whereas the cell end facing the S2 anode became more negative intracellularly. The S2-induced transmembrane potential change at the cell end (ΔV(m)) was determined relative to the amplitude of the S1-induced action potential (APA) in each recording (i.e., ΔV(m)/APA). In Tyrode's solution containing 4.5 mM potassium, ΔV(m)/APA for 40-V/cm S2 was 1.36±0.34 at the cell end facing the S2 cathode and - 1.65±0.61 at the cell end facing the S2 anode (n=9). For the 20-V/cm S2, ΔV(m)/APA was 0.61±0.33 at the cell end facing the S2 cathode and - 0.71±0.33 at the cell end facing the S2 anode (n=6). The ΔV(m)/APA was not significantly influenced by 20 mM diacetyl monoxime. These results indicate that large ΔV(m) values occurred at the ends of the cells during S2. The calculated values of ΔV(m), assuming a nominal APA of 130 mV, were 177 and - 214 mV for the 40-V/cm S2 and 79 and -93 mV for the 20-V/cm S2. The ΔV(m) was correlated with cell size (r≥0.95) and agreed with values predicted by the S2 electric field strength multiplied by half of the cell length to within 27%. When the potassium concentration was increased to 20 mM, ΔV(m)/APA for 40 V/cm S2 increased 85% and 67% at the cell ends facing the S2 cathode and anode, respectively (n=9, p<0.005 versus 4.5 mM potassium), consistent with reduced APA. Thus, with normal or elevated extracellular potassium, transmembrane potential changes at the ends of cells during defibrillation-type stimulation are large enough to produce activation or recovery of voltage-dependent ion channels and may produce the effects responsible for defibrillation.
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    Author List

  • Knisley SB; Blitchington TF; Hill BC; Grant AO; Smith WM; Pilkington TC; Ideker RE
  • Start Page

  • 255
  • End Page

  • 270
  • Volume

  • 72
  • Issue

  • 2