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 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.


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
These data suggested that the decreased L-type Ca(2+) current in antral SMCs may contribute to antral hypomotility in STZ-induced diabetic rats.
Veterans Research and Education Foundation, VA Medical Center, Oklahoma City, OK, USA.
S
S
Li
J D Z
JD
Chen
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism / Q000502:physiology*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology*; D005746:Gastric Emptying / Q000187:drug effects / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D014700:Verapamil; D002118:Calcium
L-type; calcium channel; calcium channel blocker; diabetes; gastric emptying; smooth muscle cell