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

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. •Hydrocortisone decreased QT interval and action potential duration in cardiomyocytes.•Hydrocortisone reduced amplitude of contraction and Ca2+ transient in cardiomyocytes.•Hydrocortisone increased hERG K+ current and decreased Kv1.5 K+ current.•PKC inhibitor prevented the effects of hydrocortisone on cardiac electrophysiology.•Hydrocortisone activated PKCα/βII and PKCε in cardiomyocytes.