title: Restoration of the response of the middle cerebral artery of the rat to acidosis in hyposmotic hyponatremia by the opener of large-conductance calcium sensitive potassium channels (BKCa).
abstract: Hyposmotic hyponatremia (the decrease of extracellular concentration of sodium ions from 145 to 121 mM and the decrease of hyposmolality from 300 to 250 mOsm/kg H2O) impairs response of the middle cerebral artery (MCA) to acetylcholine and NO donor (S-nitroso-N-acetyl-DL-penicillamine). Since acidosis activates a similar intracellular signaling pathway, the present study was designed to verify the hypothesis that the response of the MCA to acidosis is impaired during acute hyposmotic hyponatremia due to abnormal NO-related signal transduction in vascular smooth muscle cells. Studies performed on isolated, cannulated, and pressurized rat MCA revealed that hyposmotic hyponatremia impaired the response of the MCA to acidosis and this was associated with hyposmolality rather than with decreased sodium ion concentration. Response to acidosis was restored by the BKCabut not by the KATPchannel activator. Patch-clamp electrophysiology performed on myocytes freshly isolated from MCAs, demonstrated that hyposmotic hyponatremia does not affect BKCacurrents but decreases the voltage-dependency of the activation of the BKCachannels in the presence of a specific opener of these channels. Our study suggests that reduced sensitivity of BKCachannels in the MCA to agonists results in the lack of response of this artery to acidosis during acute hyposmotic hyponatremia.
authors.affiliation: 1 Department of Neurosurgery, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Aleksandrowicz
authors.affiliation: 2 Department of Biophysics, Warsaw University of Life Sciences, Warsaw, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Dworakowska
authors.affiliation: 2 Department of Biophysics, Warsaw University of Life Sciences, Warsaw, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Dolowy
authors.affiliation: 1 Department of Neurosurgery, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.|3 Department of Experimental and Clinical Physiology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Kozniewska
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000138:Acidosis / Q000378:metabolism / Q000503:physiopathology*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D007010:Hyponatremia / Q000378:metabolism / Q000503:physiopathology*; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D020768:Middle Cerebral Artery / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D032342:Muscle Cells / Q000187:drug effects / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D009569:Nitric Oxide / Q000096:biosynthesis; D020030:Nitric Oxide Donors / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D017208:Rats, Wistar; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
chemical_list: D001562:Benzimidazoles; D051036:Large-Conductance Calcium-Activated Potassium Channels; D020030:Nitric Oxide Donors; C086491:NS 1619; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D000109:Acetylcholine
keywords: Acidosis; hyposmotic hyponatremia; isolated middle cerebral artery; large-conductance Ca2+ sensitive K+ channels; myocytes