Modulation of the rat middle cerebral artery response to acidosis in hyponatremia by the opener of large-conductance calcium-dependent potassium channels (BKCa)

• Autorzy: Aleksandrowicz M. , Kozniewska E.
• Języki publikacji: EN

Abstrakty

EN

Objectives: It is well known, that acidosis-induced dilation of the middle cerebral artery (MCA) in normonatremia depends on BKCa channel activation in smooth muscle cells of the arterial wall. Our studies on the effect of hyponatremia on the regulation of the rat MCA have demonstrated, that acute hyponatremia causes BKCa channel dysfunction manifested by its reduced sensitivity to agonists. The aim of our present experiments was, therefore, to study whether the response of MCA to acidosis is decreased during hyponatremia and if so, whether BKCa channel activator applied in subthreshold dose restores the response of MCA to lowering of extravascular pH. Method: MCAs were isolated from male Wistar rats brains and placed in the arteriograph chamber filled 3-(N-morpholino) propanesulfonic acid (MOPS) buffered saline solution containing 1% BSA. The vessels were perfused (100 µl/ min) and set at a hydrostatic pressure of 80 mmHg. The MCA images were recorded using a microscope equipped with a camera coupled to a monitor. The measured parameter was the internal diameter of the vessel. Acute hyponatremia was induced in the chamber by decreasing Na+ concentration in the extra- and intravascular fluid from 144 mM to 120 mM. After equilibration of the MCA for 1 hour in normonatremic buffer, responses of this artery to BKCa channel activator (NS1619, 10- 5M) in normo- and hyponatremia, to lowering of extravascular pH from 7.4 to 7.0 in normonatremia, in hyponatremia and in hyponatremia in the presence of NS1619 (10-5M) were studied. Results: NS1619 administration led to MCA dilation by 16 ± 1% (P<0.001) in normonatremia but had no effect on the vessel diameter in hyponatremia. Reducing pH from 7.4 to 7.0 resulted in the dilation of MCA by 18 ± 2% (P<0.001) in normonatremia whereas in hyponatremia constriction of the MCA by 4 ± 2% (P<0.01) in response to reduced pH was observed. The presence of BKCa channel activator restored the response of the MCA to acidosis during hyponatremia. Conclusion: These results confirm our previous findings that during acute hyponatremia, BKCa channels sensitivity in the wall of MCA is reduced. This explains lack of the dilation of this artery to extracellular acidosis in hyponatremia. This study was financially supported by statutory activities of the Mossakowski MRC PAS

Słowa kluczowe

EN

modulation; rat; middle cerebral artery response; acidosis; hyponatremia; calcium-dependent potassium channel BKCa zob.BK channel; Big Potassium zob.BK channel; Maxi-K zob.BK channel; BK channel; ion channel; large conductance; potassium ion; cell membrane

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2013
• Tom: 73
• Numer: 1
• Opis fizyczny: p.190

Twórcy

autor

Aleksandrowicz M.

• Laboratory of Experimental Neurosurgery, Department of Neurosurgery, Mossakowski Medical Research Centre, Polish Academy od Science, Warsaw, Poland

autor

Kozniewska E.

• Laboratory of Experimental Neurosurgery, Department of Neurosurgery, Mossakowski Medical Research Centre, Polish Academy od Science, Warsaw, Poland