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.
Li
Y H
YH
Department of Internal Medicine (Cardiology), University of Nebraska College of Medicine, Omaha 68189-4575.
Rozanski
G J
GJ
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