Multiple nickel-sensitive targets elicit cardiac arrhythmia in isolated mouse hearts after pituitary adenylate cyclase-activating polypeptide-mediated chronotropy.

摘要: The pituitary adenylate cyclase-activating polypeptide (PACAP)-27 modulates various biological processes, from the cellular level to function specification. However, 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 effects PACAP-27 on activity spontaneously beating isolated perfused hearts. Superfusion (20 nM) caused a significant increase baseline heart frequency in Cav2.3(+|+) (156.9 ± 10.8 239.4 ± 23.4 bpm; p < 0.01) Cav2.3(−|−) (190.3 ± 26.4 270.5 ± 25.8 p < 0.05) For Cav3.2, rate was significantly increased Cav3.2(−|−) (133.1 ± 8.5 bpm 204.6 ± 27.9 compared Cav3.2(+|+) hearts (185.7 ± 11.2 209.3 ± 22.7 bpm). While P wave duration QTc interval were following superfusion, there no effect positive chronotropic observed four study groups, as well abolished presence Ni2+ (50 μM) mice. In addition suppressing PACAP’s response, also induced conduction disturbances conclusion, most Ni2+-sensitive channels (R- T-type) may modulate PACAP signaling cascade during excitation mouse hearts, albeit lesser extent than other targets.