The acute effects of hydrocortisone on cardiac electrocardiography, action potentials, intracellular calcium, and contraction: The role of protein kinase C

Abstract

Hydrocortisone exerts adverse effects on various organs, including the heart. This study investigated the still unclear effects of hydrocortisone on electrophysiological and biochemical aspects of cardiac excitation-contraction coupling. In guinea pigs' hearts, hydrocortisone administration reduced the QT interval of ECG and the action potential duration (APD). In guinea pig ventricular myocytes, hydrocortisone reduced contraction and Ca²⁺ transient amplitudes. These reductions and the effects on APD were prevented by pretreatment with the protein kinase C (PKC) inhibitor staurosporine. In an overexpression system of Xenopus oocytes, hydrocortisone increased hERG K⁺ currents and reduced Kv1.5 K⁺ currents; these effects were negated by pretreatment with staurosporine. Western blot analysis revealed dose- and time-dependent changes in PKCα/βII, PKCε, and PKCγ phosphorylation by hydrocortisone in guinea pig ventricular myocytes. Therefore, hydrocortisone can acutely affect cardiac excitation-contraction coupling, including ion channel activity, APD, ECG, Ca²⁺ transients, and contraction, possibly via biochemical changes in PKC.

Keywords: Action potential; Ca(2+) transient; Contraction; ECG; Hydrocortisone; PKC.