Endothelin-1 and vasopressin activate Ca2+-permeable non-selective cation channels in aortic smooth muscle cells: Mechanism of receptor-mediated Ca2+ influx

Toshiaki Nakajima, Hisanori Hazama, Eji Hamada, Shen Nan Wu, Kouichi Igarashi, Takeshi Yamashita, Yousuke Seyama, Masao Omata, Yoshihisa Kurachi

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Endothelin-1 and Vasopressin Activate Ca2+-permeable Non-selective Cation Channels in Aortic Smooth Muscle Cells: Mechanism of Receptor-mediated Ca2+ Influx. Journal of Molecular and Cellular Cardiology (1996) 28, 707-722. The effects of vasopressin and endothelin-1 on cultured aortic smooth muscle cell lines (A7r5) were investigated by measurements of intracellular calcium [Ca2+]i and the patch-clamp techniques. Vasopressin and endothelin-1 (100 nM) evoked an initial peak followed by a smaller sustained rise of [Ca2+]i in the presence of extracellular calcium [Ca2+]0. In the absence of [Ca2+]0, only the initial peak of [Ca2+]0, was observed. Therefore, the initial peak of [Ca2+]i was mainly due to calcium release from the storage sites, whereas the later sustained rise of [Ca2+]i was due to the calcium entry from outside. The sustained rise of [Ca2+]i was unaffected by nifedipine (10 μM) significantly, but was completely abolished by La3+ (1 mM). Under current clamp conditions with K+-internal solution, vasopressin and endothelin-1 (100 nM) produced hyperpolarization, then followed by depolarization. Under voltage clamp conditions at a holding potential of -40 mV, both vasopressin andendothelin-1 first activated the outward current, then followed by a long-lasting inward current with a high noise level. The first outward current was abolished by charybdotoxin (100 nM), Cs+ in the patch pipette and high EGTA (10 mM) in the pipette, suggesting that it was a Ca2+-sensitive K+ current (IKCa)-The inward current was still elicited with the patch pipette containing Cs+ -internal solution, and reversed at about 0 mV. The reversal potential was not significantly altered by the replacement of [Cl-]i or [Cl-]0, proposing that the inward current is a cation selective channel (IN.S.). The inward current was also observed even when extracellular cations are Ca2+. La3+ (1 mM), Cd2+ (1 mM) completely abolished the vasopressin-induced IN.S., however, nifedipine (10 μM) failed to inhibit it significantly. Single channel activities were recorded in the cell-attached configurations when vasopressin or endothelin-1 was applied to the bathing solution. The unitary conductance of the channels was approximately 20 pS with 140 mM Na+, Cs+, or K+ in the pipette, but was 15 pS with 110 mM Ca2+ in the pipette. Permeabilities sequence calculated from the reversal potentials was Na+(Approaches the limit)Cs+(Approaches the limit)K+>Ca+. These results provide evidence that calcium entry and membrane depolarization elicited by vasopressin or endothelin-1 are mediated by a receptor-mediated Ca2+-permeable non-selective cation channel in aortic smooth muscle cells.

Original languageEnglish
Pages (from-to)707-722
Number of pages16
JournalJournal of Molecular and Cellular Cardiology
Issue number4
Publication statusPublished - 1996 Apr

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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