title: Calcium-induced calcium release in smooth muscle: loose coupling between the action potential and calcium release.
abstract: Calcium-induced calcium release (CICR) has been observed in cardiac myocytes as elementary calcium release events (calcium sparks) associated with the opening of L-type Ca(2+) channels. In heart cells, a tight coupling between the gating of single L-type Ca(2+) channels and ryanodine receptors (RYRs) underlies calcium release. Here we demonstrate that L-type Ca(2+) channels activate RYRs to produce CICR in smooth muscle cells in the form of Ca(2+) sparks and propagated Ca(2+) waves. However, unlike CICR in cardiac muscle, RYR channel opening is not tightly linked to the gating of L-type Ca(2+) channels. L-type Ca(2+) channels can open without triggering Ca(2+) sparks and triggered Ca(2+) sparks are often observed after channel closure. CICR is a function of the net flux of Ca(2+) ions into the cytosol, rather than the single channel amplitude of L-type Ca(2+) channels. Moreover, unlike CICR in striated muscle, calcium release is completely eliminated by cytosolic calcium buffering. Thus, L-type Ca(2+) channels are loosely coupled to RYR through an increase in global [Ca(2+)] due to an increase in the effective distance between L-type Ca(2+) channels and RYR, resulting in an uncoupling of the obligate relationship that exists in striated muscle between the action potential and calcium release.
authors.affiliation: Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6046, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Collier
authors.forename: G
authors.initials: G
authors.lastname: Ji
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: M I
authors.initials: MI
authors.lastname: Kotlikoff
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000502:physiology; D020013:Calcium Signaling / Q000502:physiology; D002614:Chelating Agents / Q000494:pharmacology; D015640:Ion Channel Gating / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000737:chemistry / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011817:Rabbits; D019837:Ryanodine Receptor Calcium Release Channel / Q000502:physiology; D012518:Sarcomeres / Q000737:chemistry / Q000378:metabolism; D001743:Urinary Bladder / Q000737:chemistry / Q000378:metabolism
chemical_list: D020746:Calcium Channels, L-Type; D002614:Chelating Agents; D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium