Abstract | BACKGROUND: Diabetic gastroparesis (delayed gastric emptying) is associated with antral hypomotility. L-type Ca(2+) channels play an important role in generation of action potentials and activation of contractions. This study was designed to investigate if the function of the L-type Ca(2+) channels of antral circular smooth muscle cells (SMCs) is impaired in streptozotocin (STZ)-induced diabetic rats. METHODS: Eight weeks after the injection of STZ or vehicle, whole-cell patch clamp was used to record Ca(2+) currents, and isometric tension recording was used to measure Ca(2+) influx-induced contractions in circular muscle strips. Solid gastric emptying was measured in diabetic and control rats. Protein expression of Ca(2+) αlC-subunit in antral smooth muscles was compared between diabetic and control rats. KEY RESULTS: (1) Solid gastric emptying, independent of age or bodyweight, was slower in the diabetic rats, even after acute correction of hyperglycemia. (2) Verapamil, a potent calcium channel blocker, dose dependently reduced solid gastric emptying in normal rats. (3) Current density of L-type Ca(2+) channel at 10 mV in antral circular SMCs was significantly decreased in the diabetic rats (-9.8 ± 0.7 pA/pF vs -15.9 ± 1.0 pA/pF in control, p < 0.001). However, protein expression of the Ca(2+) channel in antral muscles did not differ between diabetic and control rats. (4) Contractile responses to 1 and 3 mM [Ca(2+) ] were significantly reduced in the diabetic antral circular muscle strips, indicative of reduced Ca(2+) influx. CONCLUSIONS & INFERENCES: These data suggested that the decreased L-type Ca(2+) current in antral SMCs may contribute to antral hypomotility in STZ-induced diabetic rats.
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Authors | S Li, J D Z Chen |
Journal | Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society
(Neurogastroenterol Motil)
Vol. 26
Issue 7
Pg. 971-9
(Jul 2014)
ISSN: 1365-2982 [Electronic] England |
PMID | 24758401
(Publication Type: Journal Article)
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Copyright | © 2014 John Wiley & Sons Ltd. |
Chemical References |
- Calcium Channel Blockers
- Calcium Channels, L-Type
- Verapamil
- Calcium
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Topics |
- Action Potentials
(drug effects, physiology)
- Animals
- Calcium
(metabolism)
- Calcium Channel Blockers
(pharmacology)
- Calcium Channels, L-Type
(metabolism, physiology)
- Diabetes Mellitus, Experimental
(metabolism, physiopathology)
- Gastric Emptying
(drug effects, physiology)
- Muscle Contraction
(drug effects, physiology)
- Myocytes, Smooth Muscle
(metabolism, physiology)
- Rats
- Rats, Sprague-Dawley
- Verapamil
(pharmacology)
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