Protein kinase C potentiates stretch-induced cerebral artery tone by increasing intracellular sensitivity to Ca 2+

Abstract

The effects of PMA, an activator of protein kinase C, was studied on Ca 2+-induced tone in the rabbit basilar artery. Contractile responses to Ca 2+ occurred only in arteries pretreated with PMA; the extent of Ca 2+-induced contractions were related to the level of stretch applied to the vessels. Bay K 8644, a Ca 2+-channel agonist, at a concentration that was subthreshold for contraction, augmented the extent of Ca 2+-induced tone occurring in PMA-treated arteries. Nifedipine, a Ca 2+-entry inhibitor, and staurosporine, an inhibitor of protein kinase C attenuated the response to Ca 2+ occurring either in the absence or presence of Bay K 8644. Our results suggest that PMA increases myofilament sensitivity to Ca 2+, such that levels of Ca 2+ previously ineffective for contraction Ca 2+-influx, e.g. due to Bay K 8644, is manifest as contraction. Our results also confirm the role of extracellular Ca 2+ entry via plasma membrane stretch-dependent Ca 2+-channels in the maintenance of vascular tone in the basilar artery.