Abstract
The slow component of delayed rectifier K+ current (IKs) is essential for the repolarization process of cardiac action potential. IKs is also markedly potentiated by both α1– and β–adrenergic agonists, which is assumed to reduce excess Ca2+ influx through the simultaneously stimulated L–type Ca2+ channels by facilitating the repolarization of action potential during elevated sympathetic tone. The objective of the present study was to investigate which isoform of PKC mediates the potentiation of IKs by α1–adrenoceptor stimulation in guinea–pig atrial myocytes, using whole–cell patch-clamp method. IKs was activated by depolarizing voltage–clamp steps to various test potentials in atrial myocytes dialyzed with a control pipette solution containing 5 mM EGTA and 0.5 mM CaCl2 (free Ca2+ concentration, about 10−8 M). The stimulation of α1–adrenoceptor with 30 μM phenylephrine maximally increased the amplitude of IKs by 77.6±8.7% (n = 14). This stimulatory action of phenylephrine (30 μM) was significantly reduced (21.2±4.6% increase, n = 6) when atrial myocyte was loaded with the PKCε–selective peptide inhibitor (PKCεV1–2, 100 nM) but was minimally affected (99.1±20.7% increase, n = 6) by loading with the selective inhibitor peptide of the classical PKC isoforms (PKCβC2–4, 100 nM). These observations suggest that the novel PKC isoform PKCε is primarily involved in the α1–adrenergic potentiation of IKs in guinea–pig atrial myocytes. [Jpn J Physiol 55 Suppl:S126 (2005)]
