Objective: To determine whether cytokines alter the electrical properties of heart cells, the effects of human recombinant interleukin-1 β (IL-1) were examined in excised tissues and dissociated myocytes from Guinea pig ventricles. Methods: In a first series of experiments, transmembrane potentials were recorded from isolated papillary muscles superfused with 1 ng·ml-1 IL-1 in the absence and presence of blockers of arachidonic acid metabolism. Secondly, to examine the ionic mechanisms underlying the response to IL-1, ventricular myocytes were dissociated from collagenase perfused hearts and studied using the whole cell configuration of the patch clamp technique under conditions designed to isolate the L-type Ca2+ current (ICa). Results: In excised papillary muscles, IL-1 significantly prolonged action potential duration (measured at 90% repolarisation) by 24.2(SEM 2.2) ms and effective refractory period by 22.9(2.3) ms (both p<0.001; n=44). Other measured variables were not affected. Treatment of muscles with cyclo-oxygenase inhibitors, indomethacin (1 × 10 -5 M) or acetyl salicylic acid (2 × 10-4 M), abolished the prolongation of action potential duration elicited by IL-1. However, the effects of IL-1 were also blocked by the lipoxygenase inhibitor nordihydroguaiaretic acid (2 × 10-5 M) or by treating tissues with the leukotriene receptor blocker, ICI198615 (1 × 10-8 M). In isolated myocytes, 1 ng·ml-1 IL-1 increased ICa density in 44 of 78 cells by 33.6(7.5)% [11.7(0.6) v 14.6(0.7) pA·pF-1; p<0.001] during voltage steps from -40 to 0 mV. Conclusions: IL-1 modifies electrical properties of cardiac cells via lipid second messengers generated by cyclo-oxygenase and lipoxygenase pathways. Voltage clamp analyses suggest that these effects are mediated, at least in part, by changes in the conductance of calcium channels.Cardiovascular Research 1993;27:525-530.
- Calcium current
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Physiology (medical)