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

Abstract

1. 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. 2. 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'). 3. 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+. 4. 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. 5. 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. 6. 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 regulated arterial wall [Ca2+] through changes in membrane potential. 7. 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.