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| Myosin heavy chain isoforms in the renal microcirculation: Relationship to contractile kinetics and function |
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Professor Michael P. Walsh
Smooth Muscle Research Group, University of Calgary Faculty of Medicine, Calgary, Alberta, Canada
Canada Research Chair (Tier I) in Biochemistry
Director, CIHR Group in Regulation of Vascular Contractility |
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kCđåww@VŲiŧwæņjņK
7-2-19-20Kš
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The renal afferent and efferent arterioles regulate glomerular inflow and outflow resistances, respectively, and thereby control the pressure within the intervening glomerular capillaries (glomerular capillary pressure, PGC). Whereas the afferent arteriole must respond rapidly to increases in blood pressure, the efferent arteriole plays a distinctly different role, maintaining a tonic elevation in outflow resistance to preserve function when renal perfusion is compromised. The renal afferent arteriole exhibits an unusually rapid myogenic response and its kinetic features allow this vessel to modulate tone in response to alterations in systolic blood pressure. We examined the kinetics of angiotensin II- and norepinephrine-induced vasoconstriction in the microvasculature of the hydronephrotic kidney and found that the afferent arteriole responds ~3-fold faster than the efferent arteriole and hypothesized that this kinetic difference may be due to differential expression of myosin heavy chain isoforms. Vascular smooth muscle expresses four myosin heavy chain isoforms (MHC-1A, 1B, 2A and 2B), which are derived from a single gene by alternative splicing. MHC-1 and MHC-2 differ only at the C-terminus at the end of the myosin tail, whereas MHC-A and MHC-B differ in the absence (MHC-A) or presence (MHC-B) of a 7-amino acid insert in the ATP-binding pocket of the motor domain of the myosin head. MHC-1 and MHC-2 exhibit similar kinetic properties, but MHC-B has a higher ATPase activity and in vitro motility rate than MHC-B. We hypothesized, therefore, that MHC-B would be the predominant isoform in the afferent arteriole and MHC-A the predominant isoform in the efferent arteriole. Using RT-PCR, Western analysis and immunofluorescence imaging of isolated renal arterioles (tiny vessels that are ~one-tenth the size of a human eyelash), we found that the afferent arteriole predominantly expresses the MHC-B isoform, whereas the efferent arteriole expresses only the slower-cycling MHC-A isoform. We conclude that the myosin heavy chain expression patterns and kinetic characteristics facilitate the distinct physiological roles played by these two arterioles in regulating PGC. The renal microcirculation is, therefore, an important example of smooth muscle adaptation in regard to myosin heavy chain isoform expression and physiological function. |
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kCđåwåw@wĪČŧwęUķ―ŠqŧwuĀ
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