Regulation of arterial diameter and wall Ca2+ in cerebral arteries of rat by membrane potential and intravascular pressure

摘要

class="enumerated" style="list-style-type:decimal">The regulation of intracellular [Ca²⁺] in the smooth muscle cells in the wall of small pressurized cerebral arteries (100–200 μm) of rat was studied using simultaneous digital fluorescence video imaging of arterial diameter and wall [Ca²⁺], combined with microelectrode measurements of arterial membrane potential.Elevation of intravascular pressure (from 10 to 100 mmHg) caused a membrane depolarization from -63 ± 1 to -36 ± 2 mV, increased arterial wall [Ca²⁺] from 119 ± 10 to 245 ± 9 nm, and constricted the arteries from 208 ± 10 μm (fully dilated, Ca²⁺ free) to 116 ± 7 μm or by 45 % (‘myogenic tone’).Pressure-induced increases in arterial wall [Ca²⁺] and vasoconstriction were blocked by inhibitors of voltage-dependent Ca²⁺ channels (diltiazem and nisoldipine) or to the same extent by removal of external Ca²⁺.At a steady pressure (i.e. under isobaric conditions at 60 mmHg), the membrane potential was stable at -45 ± 1 mV, intracellular [Ca²⁺] was 190 ± 10 nm, and arteries were constricted by 41 % (to 115 ± 7 μm from 196 ± 8 μm fully dilated). Under this condition of -45 ± 5 mV at 60 mmHg, the voltage sensitivity of wall [Ca²⁺] and diameter were 7.5 nm mV⁻¹ and 7.5 μm mV⁻¹, respectively, resulting in a Ca²⁺ sensitivity of diameter of 1 μm nm⁻¹.Membrane potential depolarization from -58 to −23 mV caused pressurized arteries (to 60 mmHg) to constrict over their entire working range, i.e. from maximally dilated to constricted. This depolarization was associated with an elevation of arterial wall [Ca²⁺] from 124 ± 7 to 347 ± 12 nm. These increases in arterial wall [Ca²⁺] and vasoconstriction were blocked by L-type voltage-dependent Ca²⁺ channel inhibitors.The relationship between arterial wall [Ca²⁺] and membrane potential was not significantly different under isobaric (60 mmHg) and non-isobaric conditions (10–100 mmHg), suggesting that intravascular pressure regulates arterial wall [Ca²⁺] through changes in membrane potential.The results are consistent with the idea that intravascular pressure causes membrane potential depolarization, which opens voltage-dependent Ca²⁺ channels, acting as ‘voltage sensors’, thus increasing Ca²⁺ entry and arterial wall [Ca²⁺], which leads to vasoconstriction.