Pituitary adenylate cyclase-activating polypeptide activates KATP current in rat atrial myocytes
Pituitary adenylate cyclase-activating polypeptide activates KATP current in rat atrial myocytes
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DOI：
10.1152/ajpheart.2001.280.3.h1058
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发表时间：
2001-03-01
影响因子：
4.8
通讯作者：
Baertschi, AJ
中科院分区：
文献类型：
--
作者：
Baron, A;Monnier, D;Baertschi, AJ
由于垂体腺苷酸环化酶激活多肽（PACAP）对心脏的电生理作用知之甚少，我们研究了PACAP对原代培养的新生大鼠心房肌细胞心房atp敏感K+ (K- atp)电流的调节。PACAP-38刺激cAMP生成的EC50 = 0.28 nmol/l （r = 0.92, P < 0.02）。PACAP-38和PACAP-27 （10 nmol/l）的最大效果相似，而100 nmol/l血管活性肠多肽（VIP）的最大效果差2.7倍（P < 0.05）。RT-PCR显示存在克隆的PACAP受体PAC(1)（大于等于2个异构体）、VPAC(1)和VPAC(2)。PACAP-38剂量依赖性激活全细胞心房KATP电流，EC50 = 1-3 nmol/l （n = 44）。最大效应发生在10 nmol/l （91 +/- 15 pA/pF, n = 18）。二氮氧化物进一步使pacap激活电流增加78% （P < 0.05; n = 6）。蛋白激酶a （PKA）抑制剂H-89 （500 nmol/l）可将pacap激活的K-ATP电流降低至最大二氮氧化物诱导电流的17.8 +/- 9.6% (n = 5)，完全抑制camp诱导的K-ATP电流。移液管中的PKC抑制肽（50 mol/l）可将pacap -38诱导的K-ATP电流降低至33 +/- 17 pA/pF (P < 0.05, n = 6)，但对cAMP或VIP诱导的电流无显著影响。结果表明：1)心房肌细胞中存在PAC1、VPAC1和VPAC2；2) PACAP-38通过PKA和PKC通路激活心房KATP通道。
Because the electrophysiological effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on the heart are little known, we studied the regulation of the atrial ATP-sensitive K+ (K-ATP) current by PACAP on primary cultured neonatal rat atrial myocytes. PACAP-38 stimulates cAMP production with EC50 = 0.28 nmol/l (r = 0.92, P < 0.02). PACAP-38 and PACAP-27 (10 nmol/l) have similar maximal effects, whereas 100 nmol/l vasoactive intestinal polypeptide (VIP) is 2.7 times less effective (P < 0.05). RT-PCR shows the presence of cloned PACAP receptors PAC(1) (greater than or equal to2 isoforms), VPAC(1), and VPAC(2). PACAP-38 dose dependently activates the whole cell atrial KATP current with EC50 = 1-3 nmol/l (n = 44). Maximal effects occur at 10 nmol/l (91 +/- 15 pA/pF, n = 18). Diazoxide further increases the PACAP-activated current by 78% (P < 0.05; n = 6). H-89 (500 nmol/l), a protein kinase A (PKA) inhibitor, reduces the PACAP-activated K-ATP current to 17.8 +/- 9.6% (n = 5) of the maximal diazoxide-induced current and totally inhibits the cAMP-induced K-ATP current. A protein kinase C (PKC) inhibitor peptide (50 mol/l) in the pipette reduces the PACAP-38-induced K-ATP current to 33 +/- 17 pA/pF (P < 0.05, n = 6) without significantly affecting the currents induced by cAMP or VIP. The results suggest that: 1) PAC1, VPAC1, and VPAC2 are present in atrial myocytes; and 2) PACAP-38 activates the atrial KATP channels through both PKA and PKC pathways.