Involvement of the protein kinase C system in calcium‐force relationships in ferret aorta

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Abstract
Intracellular Ca2+‐force relationships were investigated in ferret aortic smooth muscle by the simultaneous measurement of aequorin luminescence and isometric force. Complete calcium‐force curves were constructed by plotting calibrated aequorin luminescence versus force, while intracellular [Ca2+] was made to change by increasing degrees of K+ depolarization or decreasing extracellular [Ca2+]. The steady state calcium‐force curve in response to K+ depolarization exhibited maximal force generation at an intracellular [Ca2+] of approximately 4 × 10−7 m. Further increases in intracellular [Ca2+] did not yield additional increments in force. Protein kinase C activation with the phorbol ester, 12‐deoxyphorbol‐13‐isobutyrate 20 acetate (DPBA) produced contractions accompanied by no detectable increases in aequorin luminescence. DPBA significantly shifted the control [Ca2+]‐force relationship leftward to lower intracellular [Ca2+] with an increase in the magnitude of maximal generated force. In aorta maximally precontracted by K+ depolarization, the addition of DPBA resulted in a significant increase in force in the absence of further increases in intracellular [Ca2+]. Conversely, in muscles maximally precontracted with DPBA, responses to K+ depolarization resulted in subsequent increases in force in the presence of simultaneous sustained increases in intracellular [Ca2+]. The relatively specific protein kinase C antagonist H‐7 caused a significant decrease in intrinsic myogenic tone in the absence of any statistically significant decrease in intracellular [Ca2+]. These results suggest that protein kinase C may be an important regulator of vascular smooth muscle contractility by: (1) providing a mechanism by which the apparent [Ca2+] sensitivity of the contractile apparatus during agonist‐induced contractions is increased, and (2) maintaining intrinsic myogenic tone by a mechanism the [Ca2+] requirement of which is satisfied by the resting [Ca2+]i.

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