Interleukin-1 enhances β-responsiveness of cardiac L-type calcium current suppressed by acidosis

George J Rozanski, R. C. Witt

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Modulation of the β-adrenergic control of the cardiac L-type Ca2+ current (I(Ca)) by human recombinant interleukin-1β (IL-1) was examined in guinea pig ventricular myocytes using the whole cell voltage-clamp technique. I(Ca) was evoked in Cs+-loaded myocytes by depolarizing pulses from a holding potential of -40 mV. In the presence of an acidic external solution (pH 5.8), the response of I(Ca) to isoproterenol (Iso; 0.01 and 1 μM) was markedly decreased compared with control myocytes studied at pH 7.4. However, when cells were pretreated with 1 ng/ml IL-1 and then exposed to acid media, β-responsiveness was significantly increased compared with untreated cells. Despite this effect of IL-1, maximum I(Ca) density with 0.01 and 1 μM Iso was still 51 and 58%, respectively, less than that measured at pH 7.4. The enhanced β-responsiveness produced by IL-1 was eliminated by adding amiloride to block Na+/H+ exchange or protein kinase C inhibitors staurosporine (10 nM) and calphostin C (50 nM). However, a direct activator of protein kinase C, phorbol 12-myristate 13-acetate, did not mimic the effects of the cytokine. These data demonstrate that IL-1 partially restores the β-adrenergic control of cardiac Ca2+ channels suppressed under acidic conditions. Moreover, they suggest that IL-1 acts by enhancing Na+/H+ exchange through a second messenger pathway that may involve protein kinase C. These cellular mechanisms may play a role in altering ventricular function during cytokine-mediated inflammatory processes that are initiated by myocardial ischemia.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume267
Issue number4 36-4
StatePublished - Nov 9 1994

Fingerprint

interleukin-1
acidosis
Acidosis
Interleukin-1
Calcium
calcium
protein kinase C
myocytes
Muscle Cells
Protein Kinase C
Adrenergic Agents
cytokines
Cytokines
patch-clamp technique
Staurosporine
Ventricular Function
Protein C Inhibitor
Amiloride
second messengers
Second Messenger Systems

Keywords

  • cytokines
  • protein kinase C
  • sodium ion/hydrogen ion exchange

ASJC Scopus subject areas

  • Physiology
  • Agricultural and Biological Sciences(all)

Cite this

Interleukin-1 enhances β-responsiveness of cardiac L-type calcium current suppressed by acidosis. / Rozanski, George J; Witt, R. C.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 267, No. 4 36-4, 09.11.1994.

Research output: Contribution to journalArticle

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