We investigated the role of protein kinase C (PKC) in α1-adrenergic regulation of intracellular Na+activity (aNa i) in single guinea pig ventricular myocytes. aNa i and membrane potentials were measured with the Na+-sensitive indicator sodium-binding benzofuran isophthalate and conventional microelectrodes, respectively, at room temperature (24–26°C) while myocytes were stimulated at a rate of 0.25–0.3 Hz. The PKC activator 4β-phorbol 12-myristate 13-acetate (PMA) decreased aNa i in a concentration-dependent manner. PMA (100 nM) produced a maximal decrease in aNa i of 1.5 mM from 6.5 ± 0.4 to 5.0 ± 0.4 mM (means ± SE, n = 12, P< 0.01). The PMA concentration required for a half-maximal decrease in aNa i was 0.46 ± 0.13 nM ( n = 3, P < 0.01). An inactive phorbol, 4α-phorbol 12-myristate 13-acetate, did not decrease aNa i. The decrease caused by PMA could be blocked by the PKC inhibitors staurosporine and bisindolylmaleimide I (GF-109203X). Stimulation of the α1-adrenoceptor with 50 μM phenylephrine decreased aNa i from 6.1 ± 0.3 to 4.6 ± 0.3 mM ( n = 11, P< 0.01). The decrease in aNa i produced by phenylephrine was blocked by pretreatment with staurosporine, GF-109203X, or PMA. The decrease in aNa i produced by PMA was not prevented by pretreatment with tetrodotoxin but was blocked by pretreatment with strophanthidin or high extracellular K+ concentration. The results suggest that α1-adrenergic receptor activation results in a decrease in aNa i via PKC-induced stimulation of the Na+-K+ pump in cardiac myocytes.
Hydrogen peroxide-induced c-fos expression is mediated by arachidonic acid release: role of protein kinase C
