Altered L-type Ca²⁺ channel currents in vascular smooth muscle cells from experimental diabetic rats

Abstract

Vascular complications of diabetes are associated with abnormal Ca(2+) handling by vascular smooth muscle cells (SMCs) in which the alteration in L-type voltage-dependent Ca(2+) channel (VDCC) currents may play an important role. In the present study, the characteristics of L-type VDCC currents in tail artery SMCs from streptozotocin-induced diabetic rats were examined. The densities, but not the voltage dependence, of L-type VDCC currents were reduced as diabetes progressed from 1 wk to 3 mo. The inhibitory effect of dibutyryl-cAMP on L-type VDCC currents was greater in diabetic SMCs than in age-matched control cells (P < 0.01). Both the stimulatory effect of BAY K 8644 and the inhibitory effect of nifedipine on L-type VDCC currents were significantly enhanced in diabetic cells. The diabetes-related abnormalities in L-type VDCC currents were mimicked by culturing SMCs with a high concentration of glucose. Our results suggest that the properties of L-type VDCC in diabetic vascular SMCs were significantly altered, partially related to the increased L-type VDCC sensitivity to cAMP and hyperglycemia.

Impaired Arachidonic Acid–Mediated Activation of Large-Conductance Ca2+-Activated K+ Channels in Coronary Arterial Smooth Muscle Cells in Zucker Diabetic Fatty Rats

“…In type 1 diabetic rats, the L-type Ca 2ϩ channels in vascular smooth muscle cells showed increased sensitivity to cAMP and hyperglycemia (36), and BK channel sensitivity to carbon monoxide is reduced (37). In addition, after 24 h of exposure to high glucose (23 mmol/l), rat coronary smooth muscle cells showed impaired activity in the voltage-gated K ϩ channels (4-aminopyridine sensitive) (38).…”

Diabetes-induced activation of protein kinase C inhibits store-operated Ca 2+ uptake in rat retinal microvascular smooth muscle

“…Several studies have found that KCl depolarisation-induced changes in [Ca 2+ ] i and contractions are diminished in both macrovascular and microvascular smooth muscle cells from diabetic rats [27,28,29,30,31] and this is thought to occur through a reduction in the density of voltage-dependent L-type Ca 2+ channels [32] (VDCC). In our study, the action of high K + was maintained in the retinal MVSM cells from diabetic rats suggesting that neither the VDCCs themselves nor their activation require- PKC activation (PMA).…”

Diabetes-induced changes in calcium homeostasis and the effects of calcium channel blockers in rat and mice nociceptive neurons

“…Some authors showed that in skeletal muscle cells the effectiveness of DHP under short-term application is regulated by Ca 2+ and different second messengers [11]. Others reported the changes in pharmacological sensitivity of HVA calcium channels to DHP [28].…”