PMID- 8786341
OWN - NLM
STAT- MEDLINE
DCOM- 19960926
LR  - 20190508
IS  - 0022-1295 (Print)
IS  - 1540-7748 (Electronic)
IS  - 0022-1295 (Linking)
VI  - 106
IP  - 3
DP  - 1995 Sep
TI  - Ca2+ influx pathways mediated by swelling or stores depletion in mouse 
      thymocytes.
PG  - 415-44
AB  - We used fura-2 video imaging to characterize two Ca2+ influx pathways in mouse 
      thymocytes. Most thymocytes (77%) superfused with hypoosmotic media (60% of 
      isoosmotic) exhibited a sharp, transient rise in the concentration of 
      intracellular free Ca2+ ([Ca2+]i). After a delay of approximately 70 s, these 
      swelling-activated [Ca2+]i (SWAC) transients reached approximately 650 nM from 
      resting levels of approximately 100 nM and declined from a time constant of 20 s. 
      Peak [Ca2+]i during transients correlated with maximum volume during swelling. 
      Regulatory volume decrease (RVD) was enhanced in thymocytes exhibiting SWAC 
      transients. Three lines of evidence indicate that Ca2+ influx, and not the 
      release of Ca2+ from intracellular stores, underlies SWAC transients in 
      thymocytes. First, thymocytes swollen in Ca2+-free media failed to respond. 
      Second, Gd3+ and La3+ inhibited SWAC influx with Kd's of 3.8 and 2.4 microM, 
      respectively. Finally, the depletion of Ca2+ stores with thapsigargin (TG) before 
      swelling did not inhibit the generation, nor decrease the amplitude, of SWAC 
      transients. Cell phenotyping demonstrated that SWAC transients are primarily 
      associated with immature CD4-CD8- and CD4+CD8+ thymocytes. Mature peripheral 
      lymphocytes (mouse or human) did not exhibit SWAC transients. SWAC influx could 
      be distinguished from the calcium release-activated Ca2+ (CRAC) influx pathway 
      stimulated by store depletion with TG. In TG-treated thymocytes, [Ca2+]i rose 
      steadily for approximately 100 s, peaked at approximately 900 nM, and then 
      declined slowly. Simultaneous activation of both pathways produced an additive 
      [Ca2+]i profile. Gd3+ and La3+ blocked Ca2+ entry during CRAC activation more 
      potently (Kd's of 28 and 58 nM, respectively) than Ca2+ influx during SWAC 
      transients. SWAC transients could be elicited in the presence of 1 microM Gd3+, 
      after the complete inhibition of CRAC influx. Finally, whereas SWAC transients 
      were principally restricted to immature thymocytes. TG stimulated the CRAC influx 
      pathway in all four thymic CD4/CD8 subsets and in mature T cells. We conclude 
      that SWAC and CRAC represent separate pathways for Ca2+ entry in thymocytes.
FAU - Ross, P E
AU  - Ross PE
AD  - Department of Physiology and Biophysics, University of California, Irvine 92717, 
      USA.
FAU - Cahalan, M D
AU  - Cahalan MD
LA  - eng
GR  - GM41514/GM/NIGMS NIH HHS/United States
GR  - NS14609/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Gen Physiol
JT  - The Journal of general physiology
JID - 2985110R
RN  - AU0V1LM3JT (Gadolinium)
RN  - SY7Q814VUP (Calcium)
RN  - TSN3DL106G (Fura-2)
SB  - IM
MH  - Animals
MH  - Calcium/*metabolism
MH  - Edema/*physiopathology
MH  - Female
MH  - Fura-2
MH  - Gadolinium/pharmacology
MH  - Ion Transport
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Thymus Gland/*drug effects/*metabolism
MH  - Time Factors
PMC - PMC2229265
EDAT- 1995/09/01 00:00
MHDA- 1995/09/01 00:01
PMCR- 1996/03/01
CRDT- 1995/09/01 00:00
PHST- 1995/09/01 00:00 [pubmed]
PHST- 1995/09/01 00:01 [medline]
PHST- 1995/09/01 00:00 [entrez]
PHST- 1996/03/01 00:00 [pmc-release]
AID - 96116085 [pii]
AID - 10.1085/jgp.106.3.415 [doi]
PST - ppublish
SO  - J Gen Physiol. 1995 Sep;106(3):415-44. doi: 10.1085/jgp.106.3.415.