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(Circulation Research. 2004;94:1589.)
© 2004 American Heart Association, Inc.

Cellular Biology

Effects of Electrical Shocks on Ca_i²⁺ and V_m in Myocyte Cultures

Vladimir G. Fast, Eric R. Cheek, Andrew E. Pollard, Raymond E. Ideker

From the Department of Biomedical Engineering (V.G.F., E.R.C., A.E.P., R.E.I.) and Departments of Medicine and Physiology (R.E.I.), University of Alabama at Birmingham.

Correspondence to Vladimir G. Fast, PhD, University of Alabama at Birmingham, 1670 University Blvd, VH B149, Birmingham, AL 35294. E-mail fast{at}crml.uab.edu

Changes in intracellular calcium concentration (Ca_i²⁺) induced by electrical shocks may play an important role in defibrillation, but high-resolution Ca_i²⁺ measurements in a multicellular cardiac tissue and their relationship to corresponding V_m changes (V_m) are lacking. Here, we measured shock-induced Ca_i²⁺ and V_m in geometrically defined myocyte cultures. Cell strands (width=0.8 mm) were double-stained with V_m-sensitive dye RH-237 and a low-affinity Ca_i²⁺-sensitive dye Fluo-4FF. Shocks (E5 to 40 V/cm) were applied during the action potential plateau. Shocks caused transient Ca_i²⁺ decrease at sites of both negative and positive V_m. Similar Ca_i²⁺ changes were observed in an ionic model of adult rat myocytes. Simulations showed that the Ca_i²⁺ decrease at sites of V⁺_m was caused by the outward flow of I_CaL and troponin binding; at sites of V^–_m it was caused by inactivation of I_CaL combined with extrusion by Na–Ca exchanger and troponin binding. The important role of I_CaL was supported by experiments in which application of nifedipine eliminated Ca_i²⁺ decrease at V⁺_m sites. Largest Ca_i²⁺ were observed during shocks of 10 V/cm causing simple monophasic V_m. Shocks stronger than 20 V/cm caused smaller Ca_i²⁺ and postshock elevation of diastolic Ca_i²⁺. This was paralleled with occurrence of biphasic negative V_m that indicated membrane electroporation. Thus, these data indicate that shocks transiently decrease Ca_i²⁺ at sites of both V^–_m and V⁺_m. Outward flow of I_CaL plays an important role in Ca_i²⁺ decrease in the V⁺_m areas. Very strong shocks caused smaller negative Ca_i²⁺ and postshock elevation of diastolic Ca_i²⁺, likely caused by membrane electroporation.

Key Words: defibrillation • fluorescent imaging • membrane potential • intracellular calcium

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