Limits...
The new antihypertensive drug iptakalim activates ATP-sensitive potassium channels in the endothelium of resistance blood vessels.

Wang SY, Cui WY, Wang H - Acta Pharmacol. Sin. (2015)

Bottom Line: Application of iptakalim (10 and 100 μmol/L) significantly increased the whole-cell K(ATP) currents, which were prevented by the specific K(ATP) blocker glibenclamide (1.0 μmol/L).The opening of K(ATP) channels by iptakalim depended upon the intracellular concentrations of ATP or NDPs: iptakalim activated K(ATP) channels when the intracellular ATP or NDPs were at 100 or 1000 μmol/L, and was ineffective when the non-hydrolysable ATP analogue ATPγS (1000 μmol/L) was infused into the cells.Iptakalim activates K(ATP) channels in the endothelial cells of resistance blood vessels with a low metabolic status, and this activation is dependent on both ATP hydrolysis and ATP ligands.

View Article: PubMed Central - PubMed

Affiliation: Department of Environment and Pharmacy, Tianjin Institute of Health and Environmental Medicine, Beijing 100850, China.

ABSTRACT

Aim: To investigate the mechanisms underlying the activation of ATP-sensitive potassium channels (K(ATP)) by iptakalim in cultured rat mesenteric microvascular endothelial cells (MVECs).

Methods: Whole-cell KATP currents were recorded in MVECs using automated patch clamp devices. Nucleotides (ATP, ADP and UDP) were added to the internal perfusion system, whereas other drugs were added to the cell suspension on NPC-1 borosilicate glass chips.

Results: Application of iptakalim (10 and 100 μmol/L) significantly increased the whole-cell K(ATP) currents, which were prevented by the specific K(ATP) blocker glibenclamide (1.0 μmol/L). The opening of K(ATP) channels by iptakalim depended upon the intracellular concentrations of ATP or NDPs: iptakalim activated K(ATP) channels when the intracellular ATP or NDPs were at 100 or 1000 μmol/L, and was ineffective when the non-hydrolysable ATP analogue ATPγS (1000 μmol/L) was infused into the cells. In contrast, the K(ATP) opener pinacidil activated K(ATP) channels when the intracellular concentrations of ATP or NDPs ranged from 10 to 5000 μmol/L, and even ATPγS (1000 μmol/L) was infused into the cells.

Conclusion: Iptakalim activates K(ATP) channels in the endothelial cells of resistance blood vessels with a low metabolic status, and this activation is dependent on both ATP hydrolysis and ATP ligands.

Show MeSH

Related in: MedlinePlus

Modulation of the opening effects of iptakalim and pinacidil in microvascular endothelial cells (MVECs) by ATP. The opening effects of 100 μmol/L iptakalim (Ipt, A) or pinacidil (Pin, B) were tested in the presence of MgATP, MgATPγS, or Mg-free ATP (1 mmol/L). The KATP currents were recorded in MVECs with a membrane potential of −100 mV. n=8. cP<0.01 vs control. (C) Typical recordings showed the modulatory effects of ATP on iptakalim-mediated activation.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4816240&req=5

fig3: Modulation of the opening effects of iptakalim and pinacidil in microvascular endothelial cells (MVECs) by ATP. The opening effects of 100 μmol/L iptakalim (Ipt, A) or pinacidil (Pin, B) were tested in the presence of MgATP, MgATPγS, or Mg-free ATP (1 mmol/L). The KATP currents were recorded in MVECs with a membrane potential of −100 mV. n=8. cP<0.01 vs control. (C) Typical recordings showed the modulatory effects of ATP on iptakalim-mediated activation.

Mentions: The mechanism by which ATP modulates the KATP opening effects of iptakalim was also investigated. The opening effects of iptakalim and pinacidil were compared in the presence of ATP with Mg2+, ATP without Mg2+, and ATPγS (a nonhydrolysable ATP analogue) with Mg2+. Pinacidil activated KATP in the presence of ATPγS, but iptakalim did not. Both iptakalim and pinacidil were Mg2+ dependent. These results suggest that ATP hydrolysis was necessary for iptakalim to activate KATP channels and that ATP ligands are involved in KATP activation by pinacidil (Figure 3).


The new antihypertensive drug iptakalim activates ATP-sensitive potassium channels in the endothelium of resistance blood vessels.

Wang SY, Cui WY, Wang H - Acta Pharmacol. Sin. (2015)

Modulation of the opening effects of iptakalim and pinacidil in microvascular endothelial cells (MVECs) by ATP. The opening effects of 100 μmol/L iptakalim (Ipt, A) or pinacidil (Pin, B) were tested in the presence of MgATP, MgATPγS, or Mg-free ATP (1 mmol/L). The KATP currents were recorded in MVECs with a membrane potential of −100 mV. n=8. cP<0.01 vs control. (C) Typical recordings showed the modulatory effects of ATP on iptakalim-mediated activation.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4816240&req=5

fig3: Modulation of the opening effects of iptakalim and pinacidil in microvascular endothelial cells (MVECs) by ATP. The opening effects of 100 μmol/L iptakalim (Ipt, A) or pinacidil (Pin, B) were tested in the presence of MgATP, MgATPγS, or Mg-free ATP (1 mmol/L). The KATP currents were recorded in MVECs with a membrane potential of −100 mV. n=8. cP<0.01 vs control. (C) Typical recordings showed the modulatory effects of ATP on iptakalim-mediated activation.
Mentions: The mechanism by which ATP modulates the KATP opening effects of iptakalim was also investigated. The opening effects of iptakalim and pinacidil were compared in the presence of ATP with Mg2+, ATP without Mg2+, and ATPγS (a nonhydrolysable ATP analogue) with Mg2+. Pinacidil activated KATP in the presence of ATPγS, but iptakalim did not. Both iptakalim and pinacidil were Mg2+ dependent. These results suggest that ATP hydrolysis was necessary for iptakalim to activate KATP channels and that ATP ligands are involved in KATP activation by pinacidil (Figure 3).

Bottom Line: Application of iptakalim (10 and 100 μmol/L) significantly increased the whole-cell K(ATP) currents, which were prevented by the specific K(ATP) blocker glibenclamide (1.0 μmol/L).The opening of K(ATP) channels by iptakalim depended upon the intracellular concentrations of ATP or NDPs: iptakalim activated K(ATP) channels when the intracellular ATP or NDPs were at 100 or 1000 μmol/L, and was ineffective when the non-hydrolysable ATP analogue ATPγS (1000 μmol/L) was infused into the cells.Iptakalim activates K(ATP) channels in the endothelial cells of resistance blood vessels with a low metabolic status, and this activation is dependent on both ATP hydrolysis and ATP ligands.

View Article: PubMed Central - PubMed

Affiliation: Department of Environment and Pharmacy, Tianjin Institute of Health and Environmental Medicine, Beijing 100850, China.

ABSTRACT

Aim: To investigate the mechanisms underlying the activation of ATP-sensitive potassium channels (K(ATP)) by iptakalim in cultured rat mesenteric microvascular endothelial cells (MVECs).

Methods: Whole-cell KATP currents were recorded in MVECs using automated patch clamp devices. Nucleotides (ATP, ADP and UDP) were added to the internal perfusion system, whereas other drugs were added to the cell suspension on NPC-1 borosilicate glass chips.

Results: Application of iptakalim (10 and 100 μmol/L) significantly increased the whole-cell K(ATP) currents, which were prevented by the specific K(ATP) blocker glibenclamide (1.0 μmol/L). The opening of K(ATP) channels by iptakalim depended upon the intracellular concentrations of ATP or NDPs: iptakalim activated K(ATP) channels when the intracellular ATP or NDPs were at 100 or 1000 μmol/L, and was ineffective when the non-hydrolysable ATP analogue ATPγS (1000 μmol/L) was infused into the cells. In contrast, the K(ATP) opener pinacidil activated K(ATP) channels when the intracellular concentrations of ATP or NDPs ranged from 10 to 5000 μmol/L, and even ATPγS (1000 μmol/L) was infused into the cells.

Conclusion: Iptakalim activates K(ATP) channels in the endothelial cells of resistance blood vessels with a low metabolic status, and this activation is dependent on both ATP hydrolysis and ATP ligands.

Show MeSH
Related in: MedlinePlus