摘要

Background Diabetic gastroparesis (delayed gastric emptying) is associated with antral hypomotility. L-type Ca2+ 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 Ca2+ 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 Ca2+ currents, and isometric tension recording was used to measure Ca2+ influx-induced contractions in circular muscle strips. Solid gastric emptying was measured in diabetic and control rats. Protein expression of Ca2+lC-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 Ca2+ channel at 10mV in antral circular SMCs was significantly decreased in the diabetic rats (-9.8 +/- 0.7pA/pF vs -15.9 +/- 1.0pA/pF in control, p<0.001). However, protein expression of the Ca2+ channel in antral muscles did not differ between diabetic and control rats. (4) Contractile responses to 1 and 3mM [Ca2+] were significantly reduced in the diabetic antral circular muscle strips, indicative of reduced Ca2+ influx. Conclusions & Inferences These data suggested that the decreased L-type Ca2+ current in antral SMCs may contribute to antral hypomotility in STZ-induced diabetic rats.

  • 出版日期2014-7