Monovalent cation and L-type Ca2+ channels participate in calcium paradox-like phenomenon in rabbit aortic smooth muscle cells

摘要

class="enumerated" style="list-style-type:decimal">The effects of removal of extracellular divalent cations (experimental calcium paradox conditions) were studied on the whole-cell current in freshly isolated smooth muscle cells (SMCs), and on contraction in rabbit aortic rings.Aortic rings treated for 30–60 min with extracellular Ca²⁺- and Mg²⁺-free solution contracted following readmission of extracellular Ca²⁺, even in the presence of nifedipine.In isolated SMCs, the removal of extracellular Ca²⁺ and Mg²⁺ induced a non-inactivating whole-cell inward current and membrane depolarization. This current was a monovalent cation (MC) current which reversed at around 0 mV and conducted K⁺≥ Cs⁺ > Na⁺ > Li⁺. Extracellular divalent cations (Ca²⁺, Mg²⁺, Ba²⁺, Mn²⁺ and Ni²⁺) inhibited MC current.Using noise analysis of the whole-cell MC current, the single MC channel conductance was estimated to be < 450 fS.MC current was insensitive to nifedipine, TEA, 4-aminopyridine, SK&F 96365 and S-nitroso-N-acetyl-penicillamine (SNAP), but was decreased by amiloride and low pH.When EGTA was present in Ca²⁺- and Mg²⁺-free solution, a significant nifedipine-sensitive Na⁺ current through L-type Ca²⁺ channels developed in addition to MC current.It is concluded that upon the removal of extracellular Ca²⁺ and Mg²⁺ from resting SMCs, an inward MC current develops allowing Na⁺ influx and causing SMC depolarization which could be the important steps leading to vessel contraction upon Ca²⁺ readmission. Addition of EGTA to Ca²⁺- and Mg²⁺-free solution greatly potentiates Na⁺ influx and vessel contraction by allowing additional Na⁺ influx through L-type Ca²⁺ channels which are activated presumably by MC current-induced depolarization.