Decreased L-type calcium current in antral smooth muscle cells of STZ-induced diabetic rats

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⁺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 Ca²⁺ 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 Ca²⁺ channel in antral muscles did not differ between diabetic and control rats. (4) Contractile responses to 1 and 3 mM [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.