There is a special reason for reviewing this book at this time: it is the 50th edition of a compendium that is known and used frequently in most chemical and physical laboratories in many parts of the world. Surely, a publication that has been published for 56 years, withstanding the vagaries of science in this century, must have had something to offer. There is another reason: while the book is a standard fixture in most chemical and physical laboratories, including those in medical centers, it is not as frequently seen in the laboratories of physician's offices (those either in solo or group practice). I believe that the Handbook can be useful in those laboratories. One of the reasons, among others, is that the various basic items of information it offers may be helpful in new tests, either physical or chemical, which are continuously being published. The basic information may relate

Handbook of Chemistry and Physics

Voltage-gated Ca(2+) channels mediate Ca(2+) entry into cells in response to membrane depolarization. Electrophysiological studies reveal different Ca(2+) currents designated L-, N-, P-, Q-, R-, and T-type. The high-voltage-activated Ca(2+) channels that have been characterized biochemically are complexes of a pore-forming alpha1 subunit of approximately 190-250 kDa; a transmembrane, disulfide-linked complex of alpha2 and delta subunits; an intracellular beta subunit; and in some cases a transmembrane gamma subunit. Ten alpha1 subunits, four alpha2delta complexes, four beta subunits, and two gamma subunits are known. The Cav1 family of alpha1 subunits conduct L-type Ca(2+) currents, which initiate muscle contraction, endocrine secretion, and gene transcription, and are regulated primarily by second messenger-activated protein phosphorylation pathways. The Cav2 family of alpha1 subunits conduct N-type, P/Q-type, and R-type Ca(2+) currents, which initiate rapid synaptic transmission and are regulated primarily by direct interaction with G proteins and SNARE proteins and secondarily by protein phosphorylation. The Cav3 family of alpha1 subunits conduct T-type Ca(2+) currents, which are activated and inactivated more rapidly and at more negative membrane potentials than other Ca(2+) current types. The distinct structures and patterns of regulation of these three families of Ca(2+) channels provide a flexible array of Ca(2+) entry pathways in response to changes in membrane potential and a range of possibilities for regulation of Ca(2+) entry by second messenger pathways and interacting proteins.

Structure and regulation of voltage-gated Ca2+ channels.

In electrically nonexcitable cells, Ca2+ influx is essential for regulating a host of kinetically distinct processes involving exocytosis, enzyme control, gene regulation, cell growth and prolifera...

Store-operated calcium channels.

The family of voltage-gated sodium channels initiates action potentials in all types of excitable cells. Nine members of the voltage-gated sodium channel family have been characterized in mammals, and a 10th member has been recognized as a related protein. These distinct sodium channels have similar structural and functional properties, but they initiate action potentials in different cell types and have distinct regulatory and pharmacological properties. This article presents the molecular relationships and physiological roles of these sodium channel proteins and provides comprehensive information on their molecular, genetic, physiological, and pharmacological properties.

https://pharmrev.aspetjournals.org/content/pharmrev/57/4/411.full.pdf

International Union of Pharmacology. XLVIII. Nomenclature and Structure-Function Relationships of Voltage-Gated Calcium Channels

Repeated, intense use of muscles leads to a decline in performance known as muscle fatigue. Many muscle properties change during fatigue including the action potential, extracellular and intracellular ions, and many intracellular metabolites. A range of mechanisms have been identified that contribute to the decline of performance. The traditional explanation, accumulation of intracellular lactate and hydrogen ions causing impaired function of the contractile proteins, is probably of limited importance in mammals. Alternative explanations that will be considered are the effects of ionic changes on the action potential, failure of SR Ca2+ release by various mechanisms, and the effects of reactive oxygen species. Many different activities lead to fatigue, and an important challenge is to identify the various mechanisms that contribute under different circumstances. Most of the mechanistic studies of fatigue are on isolated animal tissues, and another major challenge is to use the knowledge generated in these studies to identify the mechanisms of fatigue in intact animals and particularly in human diseases.

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Skeletal Muscle Fatigue: Cellular Mechanisms

Voltage sensor of excitation-contraction coupling in skeletal muscle.

This is a quantitative model of control of Ca2+ release from the sarcoplasmic reticulum in skeletal muscle, based on dual control of release channels (ryanodine receptors), primarily by voltage, secondarily by Ca2+ (Rios, E., and G. Pizarro. 1988. NIPS. 3:223–227). Channels are positioned in a double row array of between 10 and 60 channels, where exactly half face voltage sensors (dihydropyridine receptors) in the transverse (t) tubule membrane (Block, B.A., T. Imagawa, K.P. Campbell, and C. Franzini-Armstrong. 1988. J. Cell Biol. 107:2587–2600). We calculate the flux of Ca2+ release upon different patterns of pulsed t-tubule depolarization by explicit stochastic simulation of the states of all channels in the array. Channels are initially opened by voltage sensors, according to an allosteric prescription (Rios, E., M. Karhanek, J. Ma, A. Gonzalez. 1993. J. Gen. Physiol. 102:449–482). Ca2+ permeating the open channels, diffusing in the junctional gap space, and interacting with fixed and mobile buffers produces defined and changing distributions of Ca2+ concentration. These concentrations interact with activating and inactivating channel sites to determine the propagation of activation and inactivation within the array. The model satisfactorily simulates several whole-cell observations, including kinetics and voltage dependence of release flux, the “paradox of control,” whereby Ca2+-activated release remains under voltage control, and, most surprisingly, the “quantal” aspects of activation and inactivation (Pizarro, G., N. Shirokova, A. Tsugorka, and E. Rios. 1997. J. Physiol. 501:289–303). Additionally, the model produces discrete events of activation that resemble Ca2+ sparks (Cheng, H., M.B. Cannell, and W.J. Lederer. 1993. Science (Wash. DC). 262:740–744). All these properties result from the intersection of stochastic channel properties, control by local Ca2+, and, most importantly, the one dimensional geometry of the array and its mesoscopic scale. Our calculations support the concept that the release channels associated with one face of one junctional t-tubule segment, with its voltage sensor, constitute a functional unit, termed the “couplon.” This unit is fundamental: the whole cell behavior can be synthesized as that of a set of couplons, rather than a set of independent channels.

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Local Control Model of Excitation–Contraction Coupling in Skeletal Muscle

The mechanism of transmission remains unclear. It is possible that release is reinforced by Ca(2+)-induced activation secondary to opening of release channels by another primary mechanism. Multiple results favor some function of IP3 in EC coupling; however, there are many arguments indicating that IP3 is not the primary transmitter. DHP receptors and ryanodine receptors are known to play essential roles in the triadic junction, but the biochemical make up of the junction has not been completely established, and there may be other essential proteins. The strongest argument in favor of mechanical coupling between voltage sensor and release channel is the close proximity of the channel protein to the T membrane and the fixed stoichiometry between sensors and channels.

Charge movement and the nature of signal transduction in skeletal muscle excitation-contraction coupling

Puzzled by recent reports of differences in specific ligand binding to muscle Ca2+ channels, we quantitatively compared the flux of Ca2+ release from the sarcoplasmic reticulum (SR) in skeletal muscle fibers of an amphibian (frog) and a mammal (rat), voltage clamped in a double Vaseline gap chamber. The determinations of release flux were carried out by the "removal" method and by measuring the rate of Ca2+ binding to dyes in large excess over other Ca2+ buffers. To have a more meaningful comparison, the effects of stretching the fibers, of rapid changes in temperature, and of changes in the Ca2+ content of the SR were studied in both species. In both frogs and rats, the release flux had an early peak followed by fast relaxation to a lower sustained release. The peak and steady values of release flux, Rp and Rs, were influenced little by stretching. Rp in frogs was 31 mM/s (SEM = 4, n = 24) and in rats 7 +/- 2 mM/s (n = 12). Rs was 9 +/- 1 and 3 +/- 0.7 mM/s in frogs and rats, respectively. Transverse (T) tubule area, estimated from capacitance measurements and normalized to fiber volume, was greater in rats (0.61 +/- 0.04 microns-1) than in frogs (0.48 +/- 0.04 micron-1), as expected from the greater density of T tubuli. Total Ca in the SR was estimated as 3.4 +/- 0.6 and 1.9 +/- 0.3 mmol/liter myoplasmic water in frogs and rats. With the above figures, the steady release flux per unit area of T tubule was found to be fourfold greater in the frog, and the steady permeability of the junctional SR was about threefold greater. The ratio Rp/Rs was approximately 2 in rats at all voltages, whereas it was greater and steeply voltage dependent in frogs, going through a maximum of 6 at -40 mV, then decaying to approximately 3.5 at high voltage. Both Rp and Rs depended strongly on the temperature, but their ratio, and its voltage dependence, did not. Assuming that the peak of Ca2+ release is contributed by release channels not in contact with voltage sensors, or not under their direct control, the greater ratio in frogs may correspond to the relative excess of Ca2+ release channels over voltage sensors apparent in binding measurements. From the marked differences in voltage dependence of the ratio, as well as consideration of Ca(2+)-induced release models, we derive indications of fundamental differences in control mechanisms between mammalian and amphibian muscle.

/pdf/ca2-release-from-the-sarcoplasmic-reticulum-compared-in-40xufarj7k.pdf

Ca2+ release from the sarcoplasmic reticulum compared in amphibian and mammalian skeletal muscle

1. Intramembrane charge movements and changes in intracellular Ca2+ concentration (Ca2+ transients) elicited by pulse depolarization were measured in frog fast twitch cut muscle fibres under voltage clamp. 2. Extracellular solutions with very low [Ca2+] and 2 mM-Mg2+ , shown in the previous paper to reduce Ca2+ release from the sarcoplasmic reticulum (SR), were found to cause two changes in charge movement: (a) a decrease (-12 nC/microF) in the charge that moves during depolarizing pulses from -90 to 0 mV, termed here 'charge 1'; (b) an increase (+7 nC/microF) in the charge moved by hyperpolarizing pulses from -90 to -180 mV, termed 'charge 2'. 3. The increase in charge moved by hyperpolarizing pulses was correlated (r = 0.64) with the decrease in charge moved by depolarizing pulses and both were correlated with the inhibition of Ca2+ release recorded in the same fibres. 4. The low Ca2+ solutions caused a shift to more negative voltages of the dependence relating charge movement and holding potential (VH). This shift is of similar magnitude (about 22 mV) and direction as the shift in the curve relating Ca2+ release flux to VH (previous paper). 5. In solutions with normal [Ca2+] a conditioning depolarization to 0 mV, of 2 s duration, placed 100 ms before a test pulse from -70 to 0 mV, reduced by 30% the amount of charge displaced by the test pulse. Conditioning pulses of 1 s or less caused potentiation of charge movement by up to 30%. 6. In low Ca2+ solutions, reduction of charge was observed at all durations of the conditioning pulse. The duration for half-inhibition was near 200 ms. 7. An extracellular solution with no metal cations caused a more radical inhibition than the low Ca2+ solutions that contained Mg2+. The inhibition of Ca2+ release was essentially complete (90-100%). The charge moved by a pulse to 0 mV was reduced by 20 nC/microF and the charge moved by a pulse to -170 mV increased 8 nC/microF. This shows that Mg2+ supports excitation-contraction (E-C) coupling to some extent. 8. A state model of the voltage sensor of E-C coupling explains qualitatively the observations in both papers.(ABSTRACT TRUNCATED AT 400 WORDS)

Gonzalo Pizarro

Papers

Voltage sensor of excitation-contraction coupling in skeletal muscle.

Local Control Model of Excitation–Contraction Coupling in Skeletal Muscle

Charge movement and the nature of signal transduction in skeletal muscle excitation-contraction coupling

Ca2+ release from the sarcoplasmic reticulum compared in amphibian and mammalian skeletal muscle

Voltage sensors of the frog skeletal muscle membrane require calcium to function in excitation‐contraction coupling.