Effects of human recombinant interleukin-1 on electrical properties of guinea pig ventricular cells.
OBJECTIVE
To determine whether cytokines alter the electrical properties of heart cells, the effects of human recombinant interleukin-1 beta (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 x 10(-5) M) or acetyl salicylic acid (2 x 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 x 10(-5) M) or by treating tissues with the leukotriene receptor blocker, ICI198615 (1 x 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.
Department of Internal Medicine (Cardiology), University of Nebraska College of Medicine, Omaha 68189-4575.
Y H
YH
Li
G J
GJ
Rozanski
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004553:Electric Conductivity; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology*; D008084:Lipoxygenase / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D010210:Papillary Muscles; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology
D007375:Interleukin-1; D011994:Recombinant Proteins; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D002118:Calcium