title: Hypoxia inhibits contraction but not calcium channel currents or changes in intracellular calcium in arteriolar muscle cells.
abstract: OBJECTIVE
  We tested the hypothesis that hypoxia inhibits currents through L-type Ca(2+) channels and inhibits norepinephrine-induced rises in intracellular Ca(2+) in cremasteric arteriolar muscle cells, thus accounting for the inhibitory effect of hypoxia on norepinephrine-induced contraction of these cells.
  
  
  METHODS
  Single smooth muscle cells were enzymatically isolated from second-order and third-order arterioles from hamster cremaster muscles. The effects of hypoxia (partial pressure of oxygen: 10-15 mm Hg) were examined on Ba(2+) (10 mM) currents through L-type Ca(2+) channels by use of the perforated patch clamp technique. Also, the effect of hypoxia on norepinephrine-induced calcium changes was studied using Fura 2 microfluorimetry.
  
  
  RESULTS
  Hypoxia inhibited the norepinephrine-induced (10 microM) contraction of single arteriolar muscle cells by 32.9 +/- 5.6% (mean +/- SE, n = 4). However, hypoxia had no significant effect on whole-cell currents through L-type Ca(2+) channels: the peak current densities measured at +20 mV were -3.83 +/- 0.40 pA/pF before hypoxia and -3.97 +/- 0.36 pA/pF during hypoxia (n = 15; p > 0.05). In addition, hypoxia did not inhibit Ca(2+) transients in arteriolar muscle cells elicited by 10 microM norepinephrine. Instead, hypoxia increased basal Ca(2+) (13.8 +/- 3.2%) and augmented peak Ca(2+) levels (29.4 +/- 7.3%) and steady-state Ca(2+) levels (15.2 +/- 5.4%) elicited by 10 microM norepinephrine (n = 21; p < 0.05).
  
  
  CONCLUSIONS
  These data indicate that hypoxia inhibits norepinephrine-induced contraction of single cremasteric arteriolar muscle cells by a mechanism that involves neither L-type Ca(2+) channels nor norepinephrine-induced Ca(2+) mobilization. Instead, our findings suggest that hypoxia must inhibit norepinephrine-induced contraction by affecting a component of the signaling pathway that lies downstream from the increases in Ca(2+) produced by this neurotransmitter.
authors.affiliation: Department of Biological Sciences, Western Michigan University, Kalamazoo, MI 49008, USA.
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Cohen
authors.forename: William F
authors.initials: WF
authors.lastname: Jackson
mesh_terms: D000818:Animals; D001160:Arterioles / Q000473:pathology; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D006224:Cricetinae; D004594:Electrophysiology; D016257:Fura-2; D000860:Hypoxia / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008564:Membrane Potentials; D008647:Mesocricetus; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000473:pathology*; D009638:Norepinephrine / Q000494:pharmacology
chemical_list: D020746:Calcium Channels, L-Type; D002118:Calcium; D016257:Fura-2; D009638:Norepinephrine