The Mitogen-Activated Protein Kinase p38-2 Is Necessary for the Inhibition of N-Type Calcium Current by Bradykinin

Calcium influx via voltage-dependent calcium channels (I Ca,V ) links depolarization of excitable cells to critical cellular processes, such as secretion, contraction, and gene transcription. Fast regulation of I Ca,V ( Ca,V by bradykinin (BK) requires the sequential activation of two G-proteins, heterotrimeric G 13 and monomeric Rac1/Cdc42. We have now defined a role in this pathway for the relatively fast-acting p38 mitogen-activated protein kinase (MAPK). The slow inhibition of I Ca,V by BK was suppressed specifically by SB203580, a compound that inhibits the p38 family of MAPKs. BK potently and selectively activated a newly discovered p38 family member, p38-2. These data provide the first evidence that a MAPK is involved in the regulation of I Ca,V by a receptor-mediated process.