L-type Ca(2+) channels and the Na(+)/Ca(2+) exchanger are the main pathways for Ca(2+) influx and efflux across the sarcolemma. The majority of Ca(2+) channels are found in couplons adjacent to ryanodine receptors, but there are at least two smaller, physically and functionally distinct, extradyadic populations. NCX is more widely dispersed in the membrane although a subpopulation is closely associated with the alpha-2 isoform of the Na(+)/K(+) ATPase and has a direct effect on ECC. In addition to Ca(2+) channels and ryanodine receptors, couplons in adult animals contain a variety of other occupants that modulate their function. These modulators can vary from one couplon to another creating a variety of molecular architectures. In this review we examine our current understanding of the molecular composition, binding partners and determinants of the localization of these proteins.