Regulation of arterial diameter and wall [Ca<sup>2+</sup>] in cerebral arteries of rat by membrane potential and intravascular pressure

Journal of Physiology - Tập 508 Số 1 - Trang 199-209 - 1998
Harm J. Knot1, Mark T. Nelson1
1Department of Pharmacology, Given Building, The University of Vermont, Burlington, VT 05405, USA

Tóm tắt

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.

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Journal of Physiology

Tập 508 Số 1

199-209

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