Premium
Calcium Spark Activity is Modulated by Perfusion Pressure in Vascular Smooth Muscle of Afferent Arterioles
Author(s) -
Yip KayPong,
Balasuramanian Lavanya,
Wang Lei,
Liu Ruisheng,
RibeiroSilva Luisa,
Sham James
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.721.16
Subject(s) - myogenic contraction , afferent arterioles , chemistry , mechanotransduction , vascular smooth muscle , depolarization , biophysics , medicine , constriction , membrane potential , anatomy , endocrinology , microbiology and biotechnology , biology , angiotensin ii , biochemistry , receptor , smooth muscle
Myogenic response and tubuloglomerular feedback are the two primary mechanisms for renal blood flow autoregulation by regulating the afferent arteriolar vascular resistance. However, the mechanisms of mechanotransduction in pressure induced myogenic response are not well defined in afferent arterioles. We have previously demonstrated that integrin‐mediated mechanical force increases the occurrence of Ca 2+ sparks in freshly isolated renal vascular smooth muscle cells (VSMCs). To test whether generation of Ca 2+ sparks is a downstream signal of mechanotransduction in pressure induced myogenic constriction, the relationship between Ca 2+ spark frequency and transmural perfusion pressure was investigated in intact VSMCs of afferent arterioles isolated from Sprague‐Dawley rats. Spontaneous Ca 2+ sparks were found in VSMCs when afferent arterioles were perfused at 80 mmHg. The Ca 2+ spark frequency was significantly increased when perfusion pressure was increased by 40 mmHg. Similar increase of Ca 2+ spark frequency was also found when arterioles were stimulated with β 1 ‐integrin activating antibody. Spontaneous membrane current recorded with whole cell perforated‐patch in renal VSMCs indicated that there were more spontaneous transient inward currents (STICs) than spontaneous transient outward currents (STOCs) when holding potential was set close to physiological resting membrane potential. These observations indicated that Ca 2+ sparks activity might couple to Ca 2+ ‐activated Cl − (Cl Ca ) channel and trigger pressure induced myogenic constriction via membrane depolarization. Real‐time PCR and immunofluorescence confirmed the presence of the Cl Ca channel TMEM16A in renal VSMCs. Inhibition of TMEM16A with the specific antagonist T16Ainh‐A01 impaired pressure induced myogenic contraction in the perfused afferent arterioles. It is known that myogenic response is enhanced in spontaneously hypertensive rat (SHR). TMEM16A abundance and spontaneous Ca 2+ sparks were more prevalent in renal arterioles of SHR than those of Sprague‐Dawley rats, which are consistent with notion that Ca 2+ spark activity is part of the signal transduction process in myogenic response. In conclusion, Ca 2+ sparks were detected in intact VSMCs of afferent arterioles for the first time and their frequencies were positively modulated by the perfusion pressure. The coupling Ca 2+ sparks to Cl Ca might contribute to the mechanical signal transduction process in pressure induced myogenic constriction. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .