LAUSR

Graphical abstract Figure. No Caption available. Abstract The pituitary adenylate cyclase‐activating polypeptide (PACAP)‐27 modulates various biological processes, from the cellular level to function specification. However, the cardiac actions of this neuropeptide are still under intense studies. Using control (+|+) and mice lacking (−|−) either R‐type (Cav2.3) or T‐type (Cav3.2) Ca2+ channels, we investigated the effects of PACAP‐27 on cardiac activity of spontaneously beating isolated perfused hearts. Superfusion of PACAP‐27 (20 nM) caused a significant increase of baseline heart frequency in Cav2.3(+|+) (156.9 ± 10.8 to 239.4 ± 23.4 bpm; p < 0.01) and Cav2.3(−|−) (190.3 ± 26.4 to 270.5 ± 25.8 bpm; p < 0.05) hearts. For Cav3.2, the heart rate was significantly increased in Cav3.2(−|−) (133.1 ± 8.5 bpm to 204.6 ± 27.9 bpm; p < 0.05) compared to Cav3.2(+|+) hearts (185.7 ± 11.2 bpm to 209.3 ± 22.7 bpm). While the P wave duration and QTc interval were significantly increased in Cav2.3(+|+) and Cav2.3(−|−) hearts following PACAP‐27 superfusion, there was no effect in Cav3.2(+|+) and Cav3.2(−|−) hearts. The positive chronotropic effects observed in the four study groups, as well as the effect on P wave duration and QTc interval were abolished in the presence of Ni2+ (50 &mgr;M) and PACAP‐27 (20 nM) in hearts from Cav2.3(+|+) and Cav2.3(−|−) mice. In addition to suppressing PACAP’s response, Ni2+ also induced conduction disturbances in investigated hearts. In conclusion, the most Ni2+‐sensitive Ca2+ channels (R‐ and T‐type) may modulate the PACAP signaling cascade during cardiac excitation in isolated mouse hearts, albeit to a lesser extent than other Ni2+‐sensitive targets.