[Show abstract][Hide abstract] ABSTRACT:
Propofol has the side effect of hypotension especially in the elderly and patients with hypertension. Previous studies suggest propofol-caused hypotension results from activation of large conductance Ca(2+)-sensitive K channels (BKCa). In this study, the effects of propofol on the Ca(2+) sensitivity of BKCa were investigated in mice cerebral arterial smooth muscle cells.
Single smooth muscle cells were prepared from the cerebral arteries of mice. Perforated whole-cell recoding was conducted to investigate the whole-cell BKCa current and spontaneous transient outward K(+) current (STOC). Inside-out patch configuration was used to record the single channel current and to study the Ca(2+)- and voltage-dependence of BKCa.
Propofol (56 and 112 μmol/L) increased the macroscopic BKCa and STOC currents in a concentration-dependent manner. It markedly increased the total open probability (NPo) of single BKCa channel with an EC(50) value of 76 μmol/L. Furthermore, propofol significantly decreased the equilibrium dissociation constant (K(d)) of Ca(2+) for BKCa channel. The K(d) value of Ca(2+) was 0.881 μmol/L in control, and decreased to 0.694, 0.599 and 0.177 μmol/L, respectively, in the presence of propofol 28, 56 and 112 μmol/L. An analysis of the channel kinetics revealed that propofol (112 μmol/L) significantly increased the open dwell time and decreased the closed dwell time, which stabilized BKCa channel in the open state.
Propofol increases the Ca(2+) sensitivity of BKCa channels, thus lowering the Ca(2+) threshold of the channel activation in arterial smooth muscle cells, which causes greater vasodilating effects.