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

1. 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. 2. 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. 3. 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. 4. Using noise analysis of the whole-cell MC current, the single MC channel conductance was estimated to be < 450 fS. 5. 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. 6. 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. 7. 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.