Protein kinase C potentiates stretch-induced cerebral artery tone by increasing intracellular sensitivity to Ca2+

The effects of PMA, an activator of protein kinase C, was studied on Ca2+-induced tone in the rabbit basilar artery. Contractile responses to Ca2+ occurred only in arteries pretreated with PMA; the extent of Ca2+-induced contractions were related to the level of stretch applied to the vessels. Bay K 8644, a Ca2+-channel agonist, at a concentration that was subthreshold for contraction, augmented the extent of Ca2+-induced tone occurring in PMA-treated arteries. Nifedipine, a Ca2+-entry inhibitor, and staurosporine, an inhibitor of protein kinase C attenuated the response to Ca2+ occurring either in the absence or presence of Bay K 8644. Our results suggest that PMA increases myofilament sensitivity to Ca2+, such that levels of Ca2+ previously ineffective for contraction Ca2+-influx, e.g. due to Bay K 8644, is manifest as contraction. Our results also confirm the role of extracellular Ca2+ entry via plasma membrane stretch-dependent Ca2+-channels in the maintenance of vascular tone in the basilar artery.