The Universal Intracellular Messenger, Calcium ( Ca2 + )

The second experiment sought to determine whether calcium entry is via L-type calcium channels, therefore, verapamil (10-5 M) was used to block these channels. The tissue was then stimulated using 0.2ml of Ach (10-5 M) and K+-depolarising solution.

Calcium plays a very significant role in our bodies. Approximately 99 percent of the calcium in our bodies is stored in the teeth and bones. Calcium generates about two percent of our total body weight. Calcium is crucial in bone formation, keeping strong bones and teeth and is known for helping to prevent osteoporosis. Although calcium is mostly thought about in the bones and teeth, it also plays important roles throughout the body. The amount of calcium outside the bones and teeth may be small in comparison to what is inside the bones and teeth, but is very useful in many functions in the body. Calcium is required in functions such as the contraction

This experiment seeks to analyze how the resting membrane potential of Orconectes rusticus muscle cells changes in response to increasing [K+]o solution concentrations. By recording the intracellular voltage of the DEM, DEL1, and DEL2 crayfish muscle cells at six concentrations of [K+]o solution, we determined whether the observed resting membrane potentials (Vrest) were significantly different from the predicted Nernst equilibrium potential values. We hypothesized that the Vrest of the crayfish muscles at each concentration would not significantly differ from the Nernst potential, which solely considers the permeability of potassium ions to the cell membrane. However, our findings suggested differently, and results indicated that the Nernst equation did not accurately predict the obtained values of the resting membrane potential. The differences in muscle cell Vrest reveal instead that the membrane is differentially permeable to other ions.

Voltage gated channels are necessary components of life processes, in many organisms. One in particular, is the calcium voltage gated ion channel. Often lodged within the phospholipid bilayer, the imbalance of the calcium, or, the inside vs outside concentration, creates a gradient. The channel proteins often undergo conformations, states that which allow or block calcium ions from passing through. As ions move inside the cell, this creates a depolarization, or surge in the voltage. Clinically, this is associated with the heart and how it allows the heart to contract, which can be read in the

Changes in the concentration of small molecules, called second messengers, constitute the next step in the molecular information circuit. Particularly important second messengers include cyclic AMP and cyclic GMP, calcium ion, inositol 1,4,5-trisphosphate, (IP3), and diacylglycerol. The use of second messengers has several consequences. First, second messengers are often free to diffuse to other compartments of the cell, such as the nucleus, where they can influence gene expression and other processes. Second, the signal may be amplified significantly in the generation of second messengers. Enzymes or membrane channels are almost always activated in second-messenger generation; each activated macromolecule can lead to the generation of many second messengers within the cell. Thus, a low concentration of the signal in the environment, even as little as a single molecule, can yield a large intracellular signal and response. Third, the use of common second messengers in multiple signaling pathways creates both opportunities and possible problems. Input from several signaling pathways, often called cross talk, may affect the concentrations of common second messengers. Cross talk permits more finely tuned regulation of cell activity than would the action of individual independent pathways. However, unsuitable cross talk can cause second messengers to be

Calcium needs to be released first and needs to be obtained in the body in order for the body to carry out its function. Calcium or calcium ion (Ca2+) is stored in the sacroplasmic reticulum (SR) to start contraction for the muscles.11 In the case of the cardiac muscle, it would start contraction through the Sodium-Calcium exchange (NCX) and with limited help of the SR. Sodium ions (Na+) would enter from the dyadic cleft, the space where the cell membrane and SR are in close proximity.11 This would cause Ca2+ to flow out of the cell. In order for Ca2+ to reenter it has to go through Ca2+ channels and so Ca2+ would be released.11 Excitation-contraction coupling relies on the dyadic cleft of Ca2+ to be released. Understanding how NCX works could help provide treatment for HF because the cardiac muscle could be manipulated to contract. It may be possible to remove the NCX because it can cause too much Ca2+ to be stored in the SR and cause arrhythmias and cell death.11 This would lead to a pathway to fixing any heart failure

The ability of HVA Ca2+ channels to alter the firing pattern of postsynaptic neurons makes regulation of HVA Ca2+ channels a means to help prevent hypersynchronis neuronal activity and prevent epileptic seizures. The synaptic vesicle protein 2A (SV2A) is a protein in neurons that is important for calcium-regulated secretion of neurotransmitters (6). The protein SV2A regulates neurotransmitter release by affecting the expression of the Ca2+ sensor protein synaptotagmin, by reducing Ca2+-mediated vesicle exocytosis and thereby reducing neurotransmitter release (6). The ability of SV2A to affect synaptotagmin expression and reduce exocytosis makes regulation of SV2A binding a means to prevent abnormal neuronal activity and prevent epileptic seizures.

Influx and efflux of calcium regulate the membrane potential of the cell, which in turn regulates the contractility of smooth muscle cells. However, we neglected to link calcium’s role in membrane potential to its effects on potassium channels, one of the focuses of the first paper and the main influence on vasodilation and constriction. Furthermore, although external sources backed up the influence of insulin in activating Ca2+-ATPase as we wrote in our second hypothesis, the new supporting information does not mention insulin while suggesting that glucose might have a role in be inhibiting these Ca+-dependent K+

Starting from the top with Group I ACs, this includes ACs 1, 3, and 8, this group is stimulated by the Ca2+/calmodulin signaling pathway via direct binding of calmodulin (CAM) to the ACs.9 A majority of the evidence of stimulation comes from overexpression system studies, but current evidence on the mechanism by which the binding of CAM to AC1, 3, or 8 stimulates activity has yet to be deciphered in a cohesive manner.9 However, on the other end of the spectrum exists Group III ACs, which includes ACs 5 and 6. The Ca2+/CAM signaling pathway inhibits their activity. Structural analyses done on ACs 5 and 6 provide evidence indicating that the Ca2+ ion displaces Mg2+ ions in the active site.10 Figure 3 shows the active site with emphasis on the Asp396 and Asp440, but also shown is their interactions between a Mn2+ ion and a Mg2+ ion. The

Brain is the most complex organ in the human body. Brain and spinal cord made up part of the nervous system called central nervous system (CNS). The cerebral cortex which is the largest part of human brain has more than 100 billion of neurones, and each connected by synapses that communicate to other neurons (Pelvig DP, et al., 2008). There are several types of ion channels present along the neurons, one of these is potassium channels. Potassium channels are the integral membrane proteins that span through phospholipids bilayer of cell surface membrane which rapidly conduct potassium ions down their electrochemical gradient (Mark S.P. Sansom, et al., 2002). There are many forms of potassium channels with different functional properties. Therefore, how the tremendous diversity of potassium channels contribute well to the biological process in brain? It is vital for us to understand the important of potassium channel diversity and know benefits for the existence of the potassium channels diversity in the brain?

As Ca+ levels rise, Ca+ ions bind with Troponin which removes the blocking action of Tropomyosin

The normal cell signaling pathway of a healthy kidney includes the three Ca2+ entry pathways, the PC1/PC2, L-type/T-type, and others. PC 1 and 2 are encoding polycystins, L-type and T-type are calcium channels, and the others are also calcium channels as well. As the Ca2+ enters, it goes through P13K, which is an enzyme that is involved in cellular functions. Next, it moves on to Akt, which is a

Classical Calpains, especially those found in humans, are ubiquioltly expressed and are controlled through the inhibitor of Calpastain (Trinchese et al., 2008). Although the role of calcium inducing change to enable Calpastatin to bind to Calpain is unknown, it is seen that Calpain 2 is bounded by inhibitory domains of Calpastatin which are inhibiting Calpain from both sides of the active site cleft. From this it was assumed that Calpastatin not only recognizes that there are multiple lower affinity sites but, that they are only present in the calcium-bound form of the enzyme which results in the interaction between Calpain and Calpastatin to be tight, specific and calcium dependent (Hanna, Campbell, & Davies, 2008).

The HCO3- and Ca2+ are transported by a Na+/ HCO3- cotransporter (NBC) and a sperm-specific Ca2+ channel (CatSper). The transmembrane movement of HCO3- increases the intracellular pH. Another target of HCO3- and Ca2+ actions is the regulation of cAMP metabolism through stimulation of a unique type of adenosyl cyclase (SACY). As a consequence of SACY activation, intracellular levels of cAMP increase and activate PKA that phosphorylates various target proteins, initiating several signaling pathways leading to sperm motility activation 24,25. The beginning of slow events (Figure 4b) of capacitation occurs in the female reproductive tract and is marked by the removal of cholesterol from the membrane and the increase in its fluidity 23. The efflux of cholesterol from the sperm plasma membrane enhances bicarbonate permeability into the cell resulting in further activation of SACY, cAMP production and PKA activation. Capacitation is regulated by two parallel pathways, one requiring activation of PKA and another involving inactivation of Ser/Thr protein phosphatases, such as PP2A. Taken together, sperm capacitation results in the induction of glycolysis in the sperm tail required for the hyperativated motility. In the sperm head it causes the redistribution of surface molecules, aggregation of lipid rafts and formation of a functional ZP binding protein complex

However, direct application of Ca2+ can reduce the symptoms of Ca2+-deficiency disorder but does not remove them completely (Ferguson and Watkins 1989) and exogenous Ca2+ may not bound with the cell structure tightly that leads to easy leakage of it (Ferguson and Watkins 1983).