Role of extracellular Na+, Ca2+-activated Cl- channels and BK channels in the contraction of Ca2+ store-depleted tracheal smooth muscle.
1. In the present study, we investigated the series of events involved in the contraction of tracheal smooth muscle induced by the re-addition of Ca(2+) in an in vitro experimental model in which Ca(2+) stores had been depleted and their refilling had been blocked by thapsigargin. 2. Mean (+/-SEM) contraction was diminished by: (i) inhibitors of store-operated calcium channels (SOCC), namely 100 micromol/L SKF-96365 and 100 micromol/L 1-(2-trifluoromethylphenyl) imidazole (to 66.3 +/- 4.4 and 41.3 +/- 5.2% of control, respectively); (ii) inhibitors of voltage-gated Ca(2+) channels Ca(V)1.2 channels, namely 1 micromol/L nifedipine and 10 micromol/L verapamil (to 86.2 +/- 3.4 and 76.9 +/- 5.9% of control, respectively); and (iii) 20 micromol/L niflumic acid, a non-selective inhibitor of Ca(2+)-dependent Cl(-) channels (to 41.1 +/- 9.8% of control). In contrast, contraction was increased 2.3-fold by 100 nmol/L iberiotoxin, a blocker of the large-conductance Ca(2+)-activated K(+) (BK) channels. 3. Furthermore, contraction was significantly inhibited when Na(+) in the bathing solution was replaced by N-methyl-D-glucamine (NMDG(+)) to 39.9 +/- 7.2% of control, but not when it was replaced by Li(+) (114.5 +/- 24.4% of control). In addition, when Na(+) had been replaced by NMDG(+), contractions were further inhibited by both nifedipine and niflumic acid (to 3.0 +/- 1.8 and 24.4 +/- 8.1% of control, respectively). Nifedipine also reduced contractions when Na(+) had been replaced by Li(+) (to 10.7 +/- 3.4% to control), the niflumic acid had no effect (116.0 +/- 4.5% of control). 4. In conclusion, the data of the present study demonstrate the roles of SOCC, BK channels and Ca(V)1.2 channels in the contractions induced by the re-addition of Ca(2+) to the solution bathing guinea-pig tracheal rings under conditions of Ca(2+)-depleted sarcoplasmic reticulum and inhibition of sarcoplasmic/endoplasmic reticulum calcium ATPase. The contractions were highly dependent on extracellular Na(+), suggesting a role for SOCC in mediating the Na(+) influx.
Romero-Méndez
Catalina
C
Department of Physiology, School of Medicine, University of San Luis Potosi, San Luis Potosi, México.
Algara-Suárez
Paola
P
Sánchez-Armass
Sergio
S
Mandeville
Peter B
PB
Meza
Ulises
U
Espinosa-Tanguma
Ricardo
R
D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000502:physiology; D018118:Chloride Channels / Q000502:physiology*; D045604:Extracellular Fluid / Q000187:drug effects / Q000502:physiology; D006168:Guinea Pigs; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000502:physiology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D012964:Sodium / Q000494:pharmacology / Q000502:physiology*; D014132:Trachea / Q000187:drug effects / Q000502:physiology*
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D018118:Chloride Channels; C419385:L-type calcium channel alpha(1C); D051036:Large-Conductance Calcium-Activated Potassium Channels; D012964:Sodium; D002118:Calcium