PMID- 20204722
OWN - NLM
STAT- MEDLINE
DCOM- 20100426
LR  - 20161109
IS  - 0065-2598 (Print)
IS  - 0065-2598 (Linking)
VI  - 661
DP  - 2010
TI  - Intricate interaction between store-operated calcium entry and calcium-activated 
      chloride channels in pulmonary artery smooth muscle cells.
PG  - 31-55
LID - 10.1007/978-1-60761-500-2_3 [doi]
AB  - Ca(2+)-activated Cl-() channels (Cl(Ca)) represent an important excitatory 
      mechanism in vascular smooth muscle cells. Active accumulation of Cl-() by 
      several classes of anion transporters results in an equilibrium potential for 
      this ion about 30 mV more positive than the resting potential. Stimulation of 
      Cl(Ca) channels leads to membrane depolarization, which enhances Ca(2+) entry 
      through voltage-gated Ca(2+) channels and leads to vasoconstriction. Cl(Ca) 
      channels can be activated by distinct sources of Ca(2+) that include (1) 
      mobilization from intracellular Ca(2+) stores (ryanodine or inositol 
      1,4,5-trisphosphate [InsP(3)]) and (2) Ca(2+) entry through voltage-gated Ca(2+) 
      channels or reverse-mode Na(+)/Ca(2+) exchange. The present study was undertaken 
      to determine whether Ca(2+) influx triggered by store depletion (store-operated 
      calcium entry, SOCE) activates Cl(Ca) channels in rabbit pulmonary artery (PA) 
      smooth muscle. Classical store depletion protocols involving block of 
      sarcoplasmic reticular Ca(2+) reuptake with thapsigargin (TG; 1 microM) or 
      cyclopiazonic acid (CPA; 30 microM) led to a consistent nifedipine-insensitive 
      contraction of intact PA rings and rise in intracellular Ca(2+) concentration in 
      single PA myocytes that required the presence of extracellular Ca(2+). In patch 
      clamp experiments, TG or CPA activated a time-independent nonselective cation 
      current (I (SOC)) that (1) reversed between -10 and 0 mV; (2) displayed the 
      typical "N"-shaped current-voltage relationship; and (3) was sensitive to the (I 
      (SOC)) blocker by SKF-96365 (50 microM). In double-pulse protocol experiments, 
      the amplitude of I (SOC) was varied by altering membrane potential during an 
      initial step that was followed by a second constant step to +90 mV to register 
      Ca(2+)-activated Cl(-) current, I (Cl(Ca)). The niflumic acid-sensitive 
      time-dependent I (Cl(Ca)) at +90 mV increased in proportion to the magnitude of 
      the preceding hyperpolarizing step, an effect attributed to graded membrane 
      potential-dependent Ca(2+) entry through I (SOC) and confirmed in dual patch 
      clamp and Fluo-5 experiments to record membrane current and free intracellular 
      Ca(2+) concentration simultaneously. Reverse-transcription polymerase chain 
      reaction (RT-PCR) experiments confirmed the expression of several molecular 
      determinants of SOCE, including transient receptor potential canonical (TRPC) 1, 
      TRPC4, and TRPC6; stromal interacting molecule (STIM) 1 and 2; and Orai1 and 2, 
      as well as the novel and probable molecular candidates thought to encode for 
      Cl(Ca) channels transmembrane protein 16A (TMEM16A) Anoctamin 1 (ANO1) and B 
      (ANO2). Ourpreliminary investigation provides new evidence for a Ca(2+) entry 
      pathway consistent with store-operated Ca(2+) entry signaling that can activate 
      Ca(2+)-activated Cl-() channels in rabbit PA myocytes. We hypothesize that this 
      mechanism may be important in the regulation of membrane potential, Ca(2+) 
      influx, and tone in these cells under physiological and pathophysiological 
      conditions.
FAU - Forrest, Abigail S
AU  - Forrest AS
AD  - Department of Pharmacology, Center of Biomedical Research Excellence (COBRE), 
      University of Nevada School of Medicine, 1664 North Virginia, Reno, NV, 
      89557-0270, USA.
FAU - Angermann, Jeff E
AU  - Angermann JE
FAU - Raghunathan, Rajesh
AU  - Raghunathan R
FAU - Lachendro, Catherine
AU  - Lachendro C
FAU - Greenwood, Iain A
AU  - Greenwood IA
FAU - Leblanc, Normand
AU  - Leblanc N
LA  - eng
GR  - 5 P20 RR15581/RR/NCRR NIH HHS/United States
GR  - 5 RO1 HL 075477/HL/NHLBI NIH HHS/United States
GR  - PG/05/038/British Heart Foundation/United Kingdom
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Adv Exp Med Biol
JT  - Advances in experimental medicine and biology
JID - 0121103
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Calcium Channels)
RN  - 0 (Chloride Channels)
RN  - 0 (Chlorides)
RN  - 0 (Cyclooxygenase Inhibitors)
RN  - 0 (Indoles)
RN  - 0 (Vasodilator Agents)
RN  - 4U5MP5IUD8 (Niflumic Acid)
RN  - I9ZF7L6G2L (Nifedipine)
RN  - SY7Q814VUP (Calcium)
RN  - X9TLY4580Z (cyclopiazonic acid)
SB  - IM
MH  - Animals
MH  - Calcium/*metabolism
MH  - Calcium Channel Blockers/metabolism
MH  - Calcium Channels/genetics/*metabolism
MH  - Cells, Cultured
MH  - Chloride Channels/antagonists & inhibitors/genetics/*metabolism
MH  - Chlorides/metabolism
MH  - Cyclooxygenase Inhibitors/metabolism
MH  - Indoles/metabolism
MH  - Muscle Contraction/physiology
MH  - Muscle, Smooth, Vascular/*cytology
MH  - Myocytes, Smooth Muscle/cytology/*metabolism
MH  - Nifedipine/metabolism
MH  - Niflumic Acid/metabolism
MH  - Patch-Clamp Techniques
MH  - Pulmonary Artery/*cytology
MH  - Rabbits
MH  - Vasodilator Agents/metabolism
EDAT- 2010/03/06 06:00
MHDA- 2010/04/27 06:00
CRDT- 2010/03/06 06:00
PHST- 2010/03/06 06:00 [entrez]
PHST- 2010/03/06 06:00 [pubmed]
PHST- 2010/04/27 06:00 [medline]
AID - 10.1007/978-1-60761-500-2_3 [doi]
PST - ppublish
SO  - Adv Exp Med Biol. 2010;661:31-55. doi: 10.1007/978-1-60761-500-2_3.