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Altered smooth muscle contraction and sodium pump activity in the inflamed rat intestine
M J Muller1, J D Huizinga, S M Collins
1Intestinal Disease Research Unit, McMaster University, Hamilton, Ontario, Canada.
Abstract:
We examined changes in membrane function underlying the increased contractility of jejunal longitudinal muscle to carbachol in rats infected 6 days previously with Trichinella spiralis. Muscarinic receptor characteristics were examined in particulate fractions using [N-methyl-3H]scopolamine (NMS). There was a significant reduction in the total number of binding sites on muscle from infected rats, but the affinity for NMS was unchanged. Similarly, in competition studies, the binding of carbachol to high or low affinity sites was not significantly different in tissue from control or infected rats. However, we observed an 89% suppression of the activity of K+ -stimulated ouabain-sensitive p-nitrophenylphosphatase (pNPPase), an enzyme marker for the Na+ -K+ pump, in plasma membranes from infected compared with control rats. Similar results were obtained in 86Rb uptake studies. In contractility studies, evidence for the electrogenicity of the Na+ -K+ pump was obtained by demonstrating that pump activation by K+, Rb+, or Cs+ was associated with tissue relaxation with a rank order of potency that was identical to that for stimulation of pNPPase activity by these ions. Conversely, pump inhibition by vanadate increased tone and abolished phasic contractions in muscle from control or infected rats. This was accompanied by an increased response to carbachol in muscle from control but not infected rats. In addition, pump inhibition by removing extracellular K increased tone in control tissue but decreased tone in muscle from T. spiralis-infected rats, presumably because of preexisting pump suppression. These results are consistent with the hypothesis that suppression of electrogenic Na-pump activity contributes to the increased contractility of jejunal muscle in rats infected with T. spiralis.
Insights
Trichinella spiralis infection suppresses the Na+-K+ pump in rat jejunum, leading to increased muscle contractility. This pump dysfunction, not altered muscarinic receptors, explains heightened responses to carbachol in infected rats.
Area of Science:
- Gastrointestinal Physiology
- Parasitology
- Membrane Transport
Background:
- Trichinella spiralis infection alters host physiology.
- Jejunal longitudinal muscle shows increased contractility post-infection.
- The underlying membrane function changes require elucidation.
Purpose of the Study:
- To investigate changes in membrane function contributing to enhanced jejunal contractility in Trichinella spiralis-infected rats.
- To assess the role of muscarinic receptors and the Na+-K+ pump.
Main Methods:
- Used [N-methyl-3H]scopolamine (NMS) for muscarinic receptor binding assays.
- Measured K+-stimulated ouabain-sensitive p-nitrophenylphosphatase (pNPPase) activity and 86Rb uptake.
- Conducted contractility studies with varying ion concentrations and pump inhibitors (vanadate, K+ removal).
Main Results:
- Muscarinic receptor binding site number was reduced, but affinity was unchanged in infected rats.
- Significant suppression (89%) of Na+-K+ pump activity (pNPPase and 86Rb uptake) was observed.
- Na+-K+ pump inhibition increased carbachol response in controls but not infected rats, indicating preexisting pump suppression.
Conclusions:
- Suppression of electrogenic Na+-K+ pump activity is a key factor in the increased contractility of jejunal muscle during Trichinella spiralis infection.
- Altered Na+-K+ pump function, rather than muscarinic receptor changes, underlies the enhanced muscle response.