Impaired KATP channel function in the fetoplacental circulation of patients with type 1 diabetes mellitus

Oxygen Sensitivity, Potassium Channels, and Regulation of Placental Vascular Tone

“…Bisseling et al supported this observation that K + channels are crucial determinants of basal tone [4]; both 4AP and glibenclamide (but neither apamin nor charybdotoxin) increased perfusion pressure suggestive of a role for K V and K ATP channels (which are sensitive to oxygenation via their link to intracellular ATP levels/cell metabolism). K ATP channel activity was additionally noted to be impaired in placentas from pregnancies complicated by diabetes mellitus [4]. Functional data are summarized in Table 2.…”

“…In support of the placental perfusion data, the presence of K ATP channels was demonstrated by inhibition of agonistinduced contraction with glibenclamide [72]. Subsequent studies found reduced basal tone of chorionic plate arteries • No ↑ resistance to U46619, ET-1, and 5HT [55] • ATP-induced ↓ in resistance attenuated [55] • No change (PGI 2 induced ↓ tone) [55] • ↑ U46619-induced contraction [70] • No ↑ basal tone [9,10] • No ↑ sensitivity to SNP [70] • Relaxation in pressurized vessels [68] • Dilatation of large placental arteries [16] • No ↑ contraction to U46619 [70] • ↑ sensitivity to SNP [70] • Contraction in pressurized vessels [68] • Whole-cell I K ↓ by hypoxia [25] K v • 4AP mimics contraction effect of hypoxia [25] • 4AP ↑ perfusion pressure [4] • 4AP ↑ basal tone in control only [69] • 4AP ↑ basal tone and ET-1-induced contraction [58] • ScTX-1; MgTX; COR no basal tone effect [36] • ScTX-1; MgTX ↑ U46619-induced contraction [36] • 4AP ↑ basal tone in control only [69] • ScTX-1; MgTX; COR no basal tone effect [36] • COR ↑ U46619-induced contraction [36] • 4AP sig.…”

“…↓ I K in CPA VSMC [5] K ATP • ↑ perfusion pressure by GLIB [4] • PIN ↓ basal tone (low/control) and relaxes U46619-induced contraction (high/low; not control) [69,72] • GLIB ↓ U46619-, AVP-and ET-1-induced contraction [72] • GLIB no effect on SNAP -induced relaxation [58] • KRN2391 ↓ basal tone; ↓ U46619-induced contraction [33] • CROM no basal tone effect; desensitized U46619-induced contraction [33] • KRN4884 no basal tone effect; desensitized U46619-induced contraction [33] • PIN ↓ basal tone and ↓ U46619 contraction (high/low; not control) [69] • KRN2391 ↓ basal tone (control) and U46619-induced contraction [33] • CROM no basal tone effect; ↓ U46619-induced contraction [33] • KRN4884 no basal tone effect; ↓ U46619-induced contraction [33] • No whole-cell K ATP currents observed [25] • GLIB-sensitive alteration in VSMC but not EC V m [20] K Ca • IbTX ↓ HFPV but no effect on normoxic perfusion pressure [25] • IbTX no effect on basal tone [69] • IbTX ↑ max U46619 contraction in control only;…”

“…This may represent a physiological response to maintain a high‐flow/low‐resistance fetoplacental circulation. In placentas from pregnancies complicated by diabetes mellitus , K ATP function is also impaired. Unfortunately, the application of K ATP channel modulators to stimulate arterial/venous vasodilatation has not been documented in PE, FGR, or diabetes mellitus.…”

Expression of voltage-dependent potassium channels in first trimester human placentae

“…The presence of functional KV7 channels in human chorionic plate arteries [5], suggests a role in control of vascular tone. Perfusion studies in placental allantochorial blood vessels incubated with K + channel blockers, exhibit responses to altered oxygenation, support this further [6][7][8][9].…”