Functional Significance of Cell Volume Regulatory Mechanisms
Functional Significance of Cell Volume Regulatory Mechanisms
Functional Significance of Cell Volume Regulatory Mechanisms
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254<br />
LANG ET AL. <strong>Volume</strong> 78<br />
insertion <strong>of</strong> cell volume regulatory channels into the tion (857, 1043). Most <strong>of</strong> these channels, however, are<br />
nonselective cation channels, allowing the passage <strong>of</strong> K / plasma membrane (340, 741), in the regulation <strong>of</strong> channels<br />
,<br />
by kinases (see sect. IIIH) and phospholipids (see sect. Na / , and Ca 2/ (for review, see Refs. 682, 1043). Because <strong>of</strong><br />
IIIK), and in the activation <strong>of</strong> channels by membrane the cell-negative cell membrane potential, the respective<br />
stretch (1040). However, disruption <strong>of</strong> the actin network electrochemical gradients favor the cellular accumulation<br />
<strong>of</strong> Na / and Ca 2/ rather than cellular loss <strong>of</strong> K / did not prevent activation <strong>of</strong> channels by cell membrane<br />
. Thus<br />
stretch (1133). Furthermore, the stimulation <strong>of</strong> taurine or these channels are not likely to directly serve cell volume<br />
inositol release during cell swelling was not affected by regulation, and inhibition <strong>of</strong> these channels by gadolinium<br />
cytochalasin B (626, 848). has been shown to decrease osmotic swelling and favor<br />
The depolymerization <strong>of</strong> the actin filament network regulatory decrease <strong>of</strong> cell volume (1173). On the other<br />
may participate in the activation <strong>of</strong> a mechanosensitive hand, Ca 2/ entering the cells through these channels is<br />
thought to activate Ca 2/ -sensitive K / anion channel (832, 1108, 1227). Furthermore, depolymer-<br />
channels (187, 1194,<br />
ization <strong>of</strong> submembranous actin filaments may facilitate 1234).<br />
the fusion <strong>of</strong> channel-containing vesicle membranes with The mechanism linking membrane stretch to activa-<br />
the plasma membrane. Agonist-induced exocytosis has tion <strong>of</strong> the channels has not been clearly defined (1043).<br />
indeed been shown to be favored by actin depolymeriza- Under discussion are 1) release <strong>of</strong> fatty acids from the<br />
tion (32, 130, 147, 283, 954). stretched membrane and subsequent activation <strong>of</strong> stretch-<br />
The cytoskeleton is further thought to be involved in sensitive channels by these fatty acids (917) and 2)<br />
the volume regulatory activation <strong>of</strong> the Na / /H / exchanger stretch-induced activation <strong>of</strong> some element <strong>of</strong> the cy-<br />
(106, 404, 431, 1292), which does contain putative cytoskeleton, such as spectrin (1133). Because stretch entoskeletal<br />
binding sites (333). Actin depolymerization by hances channel open probability in the cell-free excised<br />
either cell swelling or by addition <strong>of</strong> cytochalasin B, how- patch configuration (1043), cytosolic components are ap-<br />
ever, activates the Na / -K / -2Cl 0 cotransporter (541, 586, parently not required for channel activation.<br />
813), and in vesicles devoid <strong>of</strong> cytoskeleton, the Na / -K / -<br />
2Cl<br />
It is debatable whether stretch-activated channels par-<br />
0 cotransporter is permanently active (541). This acti- ticipate in the fine-tuning <strong>of</strong> cell volume, since considerable<br />
vation is counterproductive during the initial phase <strong>of</strong> cell stretch is required to activate these channels (1043). Possi-<br />
swelling. bly, these channels may represent a last line <strong>of</strong> defense<br />
In addition to its role in regulation <strong>of</strong> ion transport, against excessive cell swelling but are not involved in the<br />
the cytoskeleton may mediate some effects <strong>of</strong> cell volume<br />
on gene expression (76, 529).<br />
response to moderate changes <strong>of</strong> cell volume.<br />
2. Microtubules<br />
D. <strong>Cell</strong> Membrane Potential<br />
<strong>Cell</strong> swelling increases microtubule stability and<br />
stimulates the expression <strong>of</strong> tubulin (511).<br />
Colchicine, which disrupts the microtubule network,<br />
inhibits RVD in Jurkat cells, HL-60 cells, and peripheral<br />
The influence <strong>of</strong> cell swelling on cell membrane po-<br />
tential depends on the ion channels preferentially activated<br />
or inactivated and on the potential difference before<br />
cell swelling. Activation <strong>of</strong> K / neutrophils (289), but not in Ehrlich ascites tumor cells<br />
(223), kidney cells (924), and gallbladder (340). In macro-<br />
phages, disruption <strong>of</strong> microtubules was found to activate<br />
anion channels (821).<br />
An intact microtubule network was found to be crucial<br />
for the influence <strong>of</strong> cell volume on alkalinization <strong>of</strong><br />
intracellular vesicles (156, 1089), proteolysis (156, 1284),<br />
and taurocholate exit from liver cells (508).<br />
channels and a low initial<br />
cell membrane potential favor hyperpolarization, whereas<br />
activation <strong>of</strong> anion or nonselective cation channels and a<br />
high initial cell membrane potential would favor depolar-<br />
ization. After cell swelling, hyperpolarization <strong>of</strong> the cell<br />
membrane is seen in hepatocytes (406), depolarization <strong>of</strong><br />
the cell membrane in Ehrlich ascites tumor cells (680,<br />
691), Madin-Darby canine kidney (MDCK) cells (947),<br />
opossum kidney cells (1235), lymphocytes (418, 419,<br />
1060), pancreatic b-cells (124), astrocytes (627), neuro-<br />
C. <strong>Cell</strong> Membrane Stretch<br />
blastoma cells (313), and vascular smooth muscle cells<br />
(685). In some cells, a transient hyperpolarization due to<br />
activation <strong>of</strong> K / A variety <strong>of</strong> ion channels are activated by cell mem-<br />
channels is followed by a more sustained<br />
brane stretch, i.e., increased tension <strong>of</strong> the cell membrane depolarization due to activation <strong>of</strong> anion channels (516–<br />
(1040, 1043). Stretch increases the open probability <strong>of</strong> the 518, 1002).<br />
channels without affecting single-channel conductance or The alteration <strong>of</strong> cell membrane potential may influselectivity<br />
<strong>of</strong> the channels (1043).<br />
ence the activity <strong>of</strong> additional ion channels. A depolariza-<br />
The stretch-activated channels may be selective for tion <strong>of</strong> the cell membrane may open voltage-sensitive ion<br />
channels. In lymphocytes, RVD involves n-type K / K chan-<br />
/ or for anions, thus directly serving cell volume regula-<br />
/ 9j07$$ja07 P18-7 12-30-97 09:41:42 pra APS-Phys Rev