Mechanism of membrane hyperpolarization by extracellular K+ in resistance-sized cerebral arterial muscle cell of rabbit

ABSTRACT

We sought to find out the mechanism of vascular relaxation by extracellular K+ concentration ((K+)o) in the cerebral resistant arteriole from rabbit. Single cells were isolated from the cerebral resistant arteriole, and using voltage-clamp technique barium-sensitive K+ currents were recorded, and their characteristics were observed. Afterwards, the changes in membrane potential and currents through the membrane caused by the change in (K+)o was observed. In the smooth muscle cells of cerebral resistant arteriole, ion currents that are blocked by barium, 4-aminopyridine (4-AP), and tetraethylammonium (TEA) exist. Currents that were blocked by barium showed inward rectification. When the (K+)o were 6, 20, 60, and 140 mM, the reversal potentials were -82.7+/-1.0, -49.5+/-1.86, -26+/-1.14, -5.18+/-1.17 mV, respectively, and these values were almost identical to the calculated K+ equilibrium potential. The inhibition of barium-sensitive inward currents by barium depended on the membrane potential. At the membrane potentials of -140, -100, and -60 mV, Kd values were 0.44, 1.19, and 4.82 muM, respectively. When (K+)o was elevated from 6 mM to 15 mM, membrane potential hyperpolarized to -50 mV from -40 mV. Hyperpolarization by K+ was inhibited by barium but not by ouabain. When the membrane potential was held at resting membrane potential and the (K+)o was elevated from 6 mM to 15 mM, outward currents increased; when elevated to 25 mM, inward currents increased. Fixing the membrane potential at resting membrane potential and comparing the barium-sensitive outward currents at (K+)o of 6 and 15 mM showed that the barium-sensitive outward current increased at 15 mM K+. From the above results the following were concluded. Barium-sensitive K+ channel activity increased when (K+)o is elevated and this leads to an increase in K+ -outward current. Consequently, the membrane potential hyperpolarizes, leading to the relaxation of resistant arteries, and this is thought to contribute to an increase in the local blood flow of brain.