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: Kenneth D Cohen, William F Jackson
• Journal: Microcirculation (New York, N.Y. : 1994) (Microcirculation) Vol. 10 Issue 2 Pg. 133-41 (Apr 2003) ISSN: 1073-9688 [Print] United States
• PMID: 12700582 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Calcium Channels, L-Type
• Calcium
• Fura-2
• Norepinephrine

Topics

• Animals
• Arterioles (pathology)
• Calcium (metabolism)
• Calcium Channels, L-Type (metabolism)
• Cricetinae
• Electrophysiology
• Fura-2
• Hypoxia (metabolism, pathology)
• Male
• Membrane Potentials
• Mesocricetus
• Muscle Contraction
• Muscle, Smooth, Vascular (pathology)
• Norepinephrine (pharmacology)