Vascular smooth muscle (VSM) cells, endothelial cells (EC), and pericytes that form the walls of vessels in the microcirculation express a diverse array of ion channels that play an important role in the function of these cells and the microcirculation in both health and disease.

Vascular tone of resistance arteries and arterioles determines peripheral vascular resistance, contributing to the regulation of blood pressure and blood flow to, and within the body’s tissues and organs. Ion channels in the plasma membrane and endoplasmic reticulum of vascular smooth muscle cells (SMCs) in these blood vessels importantly contribute to the regulation of intracellular Ca2+ concentration, the primary determinant of SMC contractile activity and vascular tone. Ion channels provide the main source of activator Ca2+ that determines vascular tone, and strongly contribute to setting and regulating membrane potential, which, in turn, regulates the open-state-probability of voltage gated Ca2+ channels (VGCCs), the primary source of Ca2+ in resistance artery and arteriolar SMCs. Ion channel function is also modulated by vasoconstrictors and vasodilators, contributing to all aspects of the regulation of vascular tone. This review will focus on the physiology of VGCCs, voltage-gated K+ (KV) channels, large-conductance Ca2+-activated K+ (BKCa) channels, strong-inward-rectifier K+ (KIR) channels, ATP-sensitive K+ (KATP) channels, ryanodine receptors (RyRs), inositol 1,4,5-trisphosphate receptors (IP3Rs), and a variety of transient receptor potential (TRP) channels that contribute to pressure-induced myogenic tone in resistance arteries and arterioles, the modulation of the function of these ion channels by vasoconstrictors and vasodilators, their role in the functional regulation of tissue blood flow and their dysfunction in diseases such as hypertension, obesity, and diabetes.

Ion channels in the plasma membrane of vascular muscle cells that form the walls of resistance arteries and arterioles play a central role in the regulation of vascular tone. Current evidence indicates that vascular smooth muscle cells express at least 4 different types of K + channels, 1 to 2 types of voltage-gated Ca 2+ channels, ≥2 types of Cl − channels, store-operated Ca + (SOC) channels, and stretch-activated cation (SAC) channels in their plasma membranes, all of which may be involved in the regulation of vascular tone. Calcium influx through voltage-gated Ca 2+, SOC, and SAC channels provides a major source of activator Ca 2+ used by resistance arteries and arterioles. In addition, K + and Cl − channels and the Ca 2+ channels mentioned previously all are involved in the determination of the membrane potential of these cells. Membrane potential is a key variable that not only regulates Ca +2 influx through voltage-gated Ca 2+ channels, but also influences release of Ca 2+ from internal stores and Ca 2+ -sensitivity of the contractile apparatus. By controlling Ca 2+ delivery and membrane potential, ion channels are involved in all aspects of the generation and regulation of vascular tone. Keywords muscle; smooth; vascular; arterioles; potassium channels; calcium channels; vascular resistance; vasoconstriction Vascular tone, the contractile activity of vascular smooth muscle cells in the walls of small arteries and arterioles, is the major determinant of the resistance to blood flow through the circulation. Thus, vascular tone plays an important role in the regulation of blood pressure and the distribution of blood flow between and within the tissues and organs of the body. Regulation of the contractile activity of vascular smooth muscle cells in the systemic circulation is dependent on a complex interplay of vasodilator and vasoconstrictor stimuli from circulating hormones, neurotransmitters, endothelium-derived factors, and blood pressure. All of these signals are integrated by vascular muscle cells to determine the activity of the contractile apparatus of the muscle cells and hence the diameter and hydraulic resistance of a blood vessel. Ion channels play a central role in this process. Like all muscle cells, vascular smooth muscle uses Ca 2+ as the trigger for contraction. Calcium influx through channels in the plasma membrane and Ca 2+ release from intracellular stores are the major source of activator Ca 2+ . In addition, the movement of ions through ion channels determines, to a large extent, membrane potential. Membrane potential, along with cytosolic Ca 2+ concentration, regulates and modulates the influx 1,2 and release 3-5 of Ca 2+ through ion channels and the sensitivity of the contractile machinery to Ca 2+.6 Vascular smooth muscle cells express ≥4 different types of K + channels, 7,8 1 to 2 types of voltage-gated Ca 2+ channels, 1,2 ≥2 types of Cl − channels, 9-11 store-operated Ca + channels, 12,13 and stretch-activated cation channels 14-16 in their plasma membranes, all of which may...

Objective To present a clear and comprehensive summary of the published data on unicompartmental knee replacement (UKA) or total knee replacement (TKA), comparing domains of outcome that have been shown to be important to patients and clinicians to allow informed decision making. Design Systematic review using data from randomised controlled trials, nationwide databases or joint registries, and large cohort studies. Data sources Medline, Embase, Cochrane Controlled Register of Trials (CENTRAL), and Clinical Trials.gov, searched between 1 January 1997 and 31 December 2018. Eligibility criteria for selecting studies Studies published in the past 20 years, comparing outcomes of primary UKA with TKA in adult patients. Studies were excluded if they involved fewer than 50 participants, or if translation into English was not available. Results 60 eligible studies were separated into three methodological groups: seven publications from six randomised controlled trials, 17 national joint registries and national database studies, and 36 cohort studies. Results for each domain of outcome varied depending on the level of data, and findings were not always significant. Analysis of the three groups of studies showed significantly shorter hospital stays after UKA than after TKA (−1.20 days (95% confidence interval −1.67 to −0.73), −1.43 (−1.53 to −1.33), and −1.73 (−2.30 to −1.16), respectively). There was no significant difference in pain, based on patient reported outcome measures (PROMs), but significantly better functional PROM scores for UKA than for TKA in both non-trial groups (standard mean difference −0.58 (−0.88 to −0.27) and −0.29 (−0.46 to −0.11), respectively). Regarding major complications, trials and cohort studies had non-significant results, but mortality after TKA was significantly higher in registry and large database studies (risk ratio 0.27 (0.16 to 0.45)), as were venous thromboembolic events (0.39 (0.27 to 0.57)) and major cardiac events (0.22 (0.06 to 0.86)). Early reoperation for any reason was higher after TKA than after UKA, but revision rates at five years remained higher for UKA in all three study groups (risk ratio 5.95 (1.29 to 27.59), 2.50 (1.77 to 3.54), and 3.13 (1.89 to 5.17), respectively). Conclusions TKA and UKA are both viable options for the treatment of isolated unicompartmental osteoarthritis. By directly comparing the two treatments, this study demonstrates better results for UKA in several outcome domains. However, the risk of revision surgery was lower for TKA. This information should be available to patients as part of the shared decision making process in choosing treatment options. Systematic review registration PROSPERO number CRD42018089972.