Hypotonically induced calcium increase and regulatory volume decrease in newborn rat cardiomyocytes

Abstract

The effect of cell swelling on intracellular calcium concentration ([Ca2+]i) was studied in newborn rat cardiomyocytes. Hypotonic cell swelling induced a fast and transient [Ca2+]i increase (hypotonically induced calcium increase, HICI; 388±47 nM, n=14). HICI was not inhibited by cyclopiazonic acid (CPA), an inhibitor of sarcoplasmic Ca2+-ATPase, nor ryanodine (an inhibitor of calcium-induced calcium release), whereas it was abolished (11±19 nM, n=5) in the absence of external calcium. Thus, HICI appeared to depend exclusively on entry of external calcium. Gadolinium ion (Gd3+), a generic inhibitor of stretch-activated cation channels (SACs), was unable to affect HICI (353±79 nM, n=6). Similarly, HICI was unaffected by internal Na+ depletion and external Na+ omission. These results suggest that neither Gd3+-sensitive SACs nor Na+-Ca2+ exchange is responsible for HICI. Conversely, HICI was inhibited by diltiazem (42±4 nM, n=3) and by membrane predepolarization (40±18 nM, n=5), suggesting an involvement of L-type voltage-activated calciumchannels. Cardiomyocyte swelling was followed by a regulatory volume decrease (RVD). The putative role of HICI in volume regulation was studied by removal of external calcium. This procedure significantly slowed RVD but did not abolish it. In conclusion, newborn rat cardiomyocytes exhibit an external-calcium-dependent HICI which contributes partially to the RVD.

Dependence of regulatory volume decrease on transient receptor potential vanilloid 4 (TRPV4) expression in human corneal epithelial cells

“…RVD is dependent on increases in plasma membrane Ca 2+ influx in various tissues [16,51,52]. We first determined whether such influx is also required for RVD in HCEC.…”

Biphasic effects of cell volume on excitation-contraction coupling in rabbit ventricular myocytes

“…Under ruptured patch voltage-clamp conditions, for example, swelling is reported to enhance I Ca-L in rabbit atrial and sinoatrial node cells (22), depress I Ca-L in rat ventricular cells (4), and to have no significant effect in guinea pig (13,31) and canine (44) ventricular cells. A swelling-induced enhancement of I Ca-L also has been claimed based on fura 2 measurements of diltiazem-sensitive Ca 2ϩ influx (36). It is unclear whether these differences in the response of I Ca-L to myocyte swelling arise from species differences or from methodological issues, such as the composition of the patch pipette solution, the effectiveness of cell dialysis, or the variable extent of myocyte swelling under ruptured-patch conditions (6,33).…”

Hyposmotic challenge modulates function of L-type calcium channel in rat ventricular myocytes through protein kinase C

“…There are controversies in the literature regarding how cell swelling can modulate cardiac I Ca,L channel. For example, I Ca,L increases in neonatal rat ventricular myocytes [14] and rabbit sinoatrial node and atrial cells [12,13] , remains unaltered in canine ventricular myocytes [17] , decreases or remains unaltered in guinea-pig ventricular myocytes [10,15] . Brette et al had reported that in rat ventricular myocytes osmotic swelling decreases I Ca,L [16] .…”

“…Some authors have even demonstrated biphasic effects on I Ca,L , an increase followed by a more sustained decrease [18] . Previous reports indicated that osmotic swelling increases I Ca,L in neonatal rat ventricular myocytes [14] , but decreases I Ca,L in adult rat ventricular myocytes [16] . But these reports did not explore the mechanism underlying the changes of I Ca,L .…”

“…However, the effect of cell swelling on cardiac I Ca,L remains controversial. For example, some studies have shown clear increases in I Ca,L [12][13][14] , while others have shown a decrease in I Ca,L [15,16] or no effect [10,17] . Some authors have even demonstrated biphasic effects on I Ca,L , an increase followed by a more sustained decrease [18] .…”