The emerging chondrocyte channelome

Abstract

Chondrocytes are the resident cells of articular cartilage and are responsible for synthesizing a range of collagenous and non-collagenous extracellular matrix macromolecules. Whilst chondrocytes exist at low densities in the tissue (1-10% of the total tissue volume in mature cartilage) they are extremely active cells and are capable of responding to a range of mechanical and biochemical stimuli. These responses are necessary for the maintenance of viable cartilage and may be compromised in inflammatory diseases such as arthritis. Although chondrocytes are non-excitable cells their plasma membrane contains a rich complement of ion channels. This diverse channelome appears to be as complex as one might expect to find in excitable cells although, in the case of chondrocytes, their functions are far less well understood. The ion channels so far identified in chondrocytes include potassium channels (K(ATP), BK, K(v), and SK), sodium channels (epithelial sodium channels, voltage activated sodium channels), transient receptor potential calcium or non-selective cation channels and chloride channels. In this review we describe this emerging channelome and discuss the possible functions of a range of chondrocyte ion channels.

Keywords: BK (MaxiK) channel; ENaC; KATP channel; Kv channel; chondrocyte.

Figure 1

Summary of the chondrocyte channelome. Many studies have now identified ion channels and porins in chondrocytes. Frequently the function of these channels is either unknown or controversial. This figure illustrates some of the major channel proteins identified to date, either by electrophysiological, immunological or molecular biological techniques. Note in this figure, K_(Ca) is taken to be equivalent to any calcium activated potassium channel including BK and SK. AQP, aquaporin channel; BK, calcium-activated potassium cannel, high conductance; ClC, chloride channel; ENaC, epithelial sodium channels; K_ATP, ATP dependent potassium channel; Kv, voltage-gated potassium channel; NMDA, N-methyl D-aspartate; SK, calcium-activated potassium channel, low conductance; TRP, transient receptor potential channel; VGCC, voltage-gated calcium channels; VGSC, voltage-gated sodium channel; This data is summarized more fully in Table 1. For references please see text and or Table 1.

Figure 2

K_ATP channels in chondrocytes. Chondrocytes have been shown to express K_ATP channels. The function of these is generally accepted to be coupling metabolic status with membrane potential and thus cell activity. In other cell types, endogenous triggers for activation of K_ATP include decrease of intracellular ATP (Babenko et al., 1998), increase in ADP (Dunne and Petersen, 1986), extracellular hypoxia (Dart and Standen, 1994) or other chemical signals such as adenosine (Dart and Standen, ; Barrett-Jolley et al., 1996), angiotensin (Sampson et al., 2007) etc., K_ATP, ATP dependent potassium channel.

Figure 3

Activation of BK by calcium ions. A number of studies have identified BK channels in chondrocytes (see text), but the function of these channels is not confirmed. Control of RMP or volume would are two theories. It is suggested that they are activated by calcium ions, which could be introduced to the cytoplasm by either release from stores, or by entry through divalent cation permeant ion channels. Both of these pathways could in turn, be activated by either mechanical or other (e.g., inflammatory) signals. ECM, extracellular matrix; Ins-P3-R, inositol trisphosphate receptor; IP3, inositol trisphosphate; K_(Ca), calcium activated potassium channels; PLC, phospholipase C; SERCA, sarco/endoplasmic reticulum Ca 2+-ATPase; TRP, transient receptor potential channel.