Ca²⁺ channels, ryanodine receptors and Ca²⁺‐activated K⁺ channels: a functional unit for regulating arterial tone

Abstract

Local calcium transients ('Ca2+ sparks') are thought to be elementary Ca2+ signals in heart, skeletal and smooth muscle cells. Ca2+ sparks result from the opening of a single, or the coordinated opening of many, tightly clustered ryanodine receptor (RyR) channels in the sarcoplasmic reticulum (SR). In arterial smooth muscle, Ca2+ sparks appear to be involved in opposing the tonic contraction of the blood vessel. Intravascular pressure causes a graded membrane potential depolarization to approximately -40 mV, an elevation of arterial wall [Ca2+]i and contraction ('myogenic tone') of arteries. Ca2+ sparks activate calcium-sensitive K+ (KCa) channels in the sarcolemmal membrane to cause membrane hyperpolarization, which opposes the pressure induced depolarization. Thus, inhibition of Ca2+ sparks by ryanodine, or of KCa channels by iberiotoxin, leads to membrane depolarization, activation of L-type voltage-gated Ca2+ channels, and vasoconstriction. Conversely, activation of Ca2+ sparks can lead to vasodilation through activation of KCa channels. Our recent work is aimed at studying the properties and roles of Ca2+ sparks in the regulation of arterial smooth muscle function. The modulation of Ca2+ spark frequency and amplitude by membrane potential, cyclic nucleotides and protein kinase C will be explored. The role of local Ca2+ entry through voltage-dependent Ca2+ channels in the regulation of Ca2+ spark properties will also be examined. Finally, using functional evidence from cardiac myocytes, and histological evidence from smooth muscle, we shall explore whether Ca2+ channels, RyR channels, and KCa channels function as a coupled unit, through Ca2+ and voltage, to regulate arterial smooth muscle membrane potential and vascular tone.

The RCK1 high-affinity Ca 2+ sensor confers carbon monoxide sensitivity to Slo1 BK channels

“…This mechanism contrasts with the redox-and heme-dependent mechanism suggested by an earlier study (36). Because the application of heme to the Slo1 BK channel decreases open probability at positive voltages (19,20), it was suggested that CO activates the channel by relieving the inhibitory effect of reduced heme (36). The relative physiological relevance of the previously proposed redox-and heme-dependent mechanism (36) and the mechanism suggested by our study is not entirely clear.…”

Local control of TRPV4 channels by AKAP150-targeted PKC in arterial smooth muscle

“…However, whereas Ca V 1.2 channels are the preponderant source of Ca 2+ for contraction, TRPV4 channels have been linked to relaxation (Harder et al, 1987;Fleischmann et al, 1994;Rubart et al, 1996;Jaggar et al, 1998;Earley et al, 2005Earley et al, , 2009Navedo et al, 2005;Amberg et al, 2007). The functional role of TRPV4 and Ca V 1.2 sparklets could be caused by differences in Ca 2+ influx through these channels in arterial myocytes.…”

Regulation of Large Conductance Ca2+-activated K+ (BK) Channel β1 Subunit Expression by Muscle RING Finger Protein 1 in Diabetic Vessels

“…Standard proteins with known molecular weights (Gel Filtration Standards, Bio-Rad Laboratories) in phosphate-buffered saline were run under the same conditions. The presence of FLAG-BK-␤1 and Myc-MuRF1 proteins in each fraction (30 l) were measured using Western blot analyses, and the band intensities were plotted against standard protein peaks (bovine thyroglobulin, 670 kDa; bovine IgG, 158 kDa; chicken ovalbumin, 44 kDa; horse myoglobin, 17 kDa, and Vitamin B 12 , 1350 Da) to estimate the size of proteins.…”