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

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Abstract

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.

Conclusions & Inferences

STZ-induced diabetes reduces the current density and induces a significant positive shift in the voltage dependence of both activation and inactivation of L-type calcium currents in antral circular smooth muscle cells, which may cause decreased calcium-induced contractions in antral smooth muscle.

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