Calcium Release Channels Recommended reading Signal Transduction ed. by Heldin and Purton Chapter 14 “Calcium Signaling” Additional extra recommended reading for those who want to learn more: Ionic Channels of Excitable membranes Bertil Hille Molecular Cell Biology pp 491 - 527 pp 536 - 544 pp 730 - 742 pp 780 - 794 Kandel, Schwartz and Jessell Principles of Neural Science 3rd Edition Chapter 5 pp 66 to 79 Chapter 8 pp 104 to 118 Appendix A pp 1033 to 1039

NCE mM [Ca] NMDA, AMPA rec nAChR CNG VR/temp rec VDAC Stretch receptor TRP mM [Ca] SOC IP3R SERCA 100 nM [Ca] ROC VGCC mM [Ca] Channels and transporters involved in maintaining ion homeostasis in cells. PMCA, plasmamembrane calcium ATPase; VGCC, voltage-gated calcium channel; ROC, receptor operatedd channel; SOC, store operated channel; TRP, transient receptor potential - channels thought to be involved in store operated calcium influx; stretch receptors, VR/temp rec, vanilloid receptors, pain and temperature sensors; CNG, cyclic nucleotide gated channels; nACHR, acetylcholine receptors; NMDA, AMPA receptors; NCE, sodium/calcium exchanger; VDAC, mitochondrial channel; IP3R, inositol 1,4,5-trisphosphate receptor; RyR, ryanodine receptor; SERCA, sarcoplasmic/endoplasmic reticular calcium ATPase. PMCA RyR SERCA

Some of the roles of calcium signaling in cells

How calcium signals may be propagated in cells

Sarcoplasmic Reticulum (SR) / T Tubule System specialized form of endoplasmic reticulum, whose membrane is rich with active transport systems (Ca-ATPase pumps) that pump intracellular calcium into the SR. Thus SR is the storage site for calcium used to activate contractile proteins. b) sac-like structure that surrounds each myofibril. c) enlarged sac at A-I band junction, lateral sacs. d) actin potential is carried to the fiber interior through the transverse tubules (i.e. t tubules). The tubule fluid is identical in composition to the extracellular fluid. The t tubules are juxtaposed to the lateral sacs. When an action potential is propagated along the t tubule, the lateral sacs are signaled by an undefined mechanism to release their calcium into the sarcoplasm, activating the contractile proteins. Summary of Excitation-Contraction Coupling Action potential at surface membrane Transmission into interior along transverse tubules Release of calcium from lateral sacs of SR Calcium diffuses to filaments and initiates contraction Calcium taken up by SR causes relaxation

Excitation-contraction coupling

Twitch Response to single action potential

Summation Increase in contractile response to a second action potential that occurs during the contractile response produced by the previous action potential.

Tetanus Response to multiple stimuli delivered at a rate sufficient to produce a fused contraction. Basis for increased force with multiple stimuli - Not due to increased release of calcium from SR, single action potential releases sufficient calcium to elicit a maximum response. Several factors act together to prevent the maximum possible force from being developed by the muscle. These factors are: a) The rapid removal of free calcium from the cytoplasm back into the SR; b) the finite time required for the troponin-tropomyosin complex to undergo conformational change before crossbridges can attach to actin c) the finite time required for crossbridges to attach to actin and then undergo the conformational change to the force generating state. Therefore, successive stimuli allow calcium to be elevated for a sufficient time so that significant crossbridge attachment and cycling can occur.

Role of Ca++ in contraction Role of Ca++ in contraction- if we deprive a muscle cell of Ca it will not contract. However, if remove the outer membrane of muscle cell, and bath "skinned fiber" in a [Ca] of 10-6 M, muscle contracts. note that muscle tension increases as [Ca] increases, and that contraction requires Mg++, and ATP.