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This Article Full Text Full Text (PDF) All Versions of this Article: 89/2/163    most recent expphysiol.2003.026732v1 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 Kettlewell, S. Articles by Smith, G. L. Search for Related Content PubMed PubMed Citation Articles by Kettlewell, S. Articles by Smith, G. L. Related Collections Heart/Cardiac Muscle

¹ Institute of Biomedical and Life Science, University of Glasgow, University Avenue, Glasgow, G12 8QQ, Scotland, UK² Section of Cardiology, Division of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow Royal Infirmary, Scotland, UK

Procedures that reduce contraction are used to facilitate optical measurements of membrane potential, but it is unclear to what extent they affect the excitability of the heart. This study has examined the electrophysiological consequences of a range of extracellular [Ca²⁺] (0.7–2.5 mmol l^–1), 2,3-butane-dione monoxime (BDM; 1–20 mmol l^–1) and cytochalasin-D (Cyto-D; 1–5 µmol l^–1). Methods. Monophasic action potentials (MAPs) were recorded from the basal epicardial surface of the left ventricle of isolated rabbit hearts. Conduction delay (CD) and time to 90% repolarisation of the monophasic action potential (MAPD₉₀) were measured. The effects of BDM and Cyto-D on restitution were studied at a [Ca²⁺] of 1.9 mmol l^–1. Restitution curves for MAPD₉₀ were generated using a standard S1–S2 protocol. Results. All manoeuvres decreased left ventricular developed pressure (LVDP): 0.7 mmol l^–1 Ca²⁺ to 74.0 ± 6.1%, 20 mmol l^–1 BDM to 4.5 ± 1.0%, and 5 µmol l^–1 Cyto-D to 12.8 ± 3.5% of control value. CD decreased from a control value (33.3 ± 1.0 ms, n= 16) to 93.0 ± 2.2% in 0.7 mmol l^–1 Ca²⁺, but increased to 133.7 ± 10.5% in 20 mmol l^–1 BDM and 127.4 ± 10.6% in 5 µmol l^–1 Cyto-D. At 350 ms pacing cycle length, MAPD₉₀ (control = 119.6 ± 1.7 ms n= 16) was prolonged by reduced extracellular [Ca²⁺]. BDM had no effects on MAPD₉₀ at control pacing rates. Cyto-D caused a significant prolongation (to 115.0 ± 3.0% of control, n= 6) at the highest concentration studied (5 µmol l^–1). Both BDM (20 mmol l^–1) and Cyto-D (3 µmol l^–1) flattened the restitution curves but neither agent altered maximum MAPD₉₀. Conclusions. Extracellular [Ca²⁺] of 1.9 mmol l^–1 in conjunction with a moderate dose of Cyto-D (3 µmol l^–1) reduced contractility with minimal effects on action potential duration and conduction at a fixed pacing cycle length. However, both BDM and Cyto-D had pronounced effects on electrical restitution.

(Received 17 October 2003; accepted after revision 3 December 2003)
Corresponding author G. L. Smith: Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, UK.  E-mail: g.smith{at}bio.gla.ac.uk