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6 Skin, The Body’s Largest Organ

One of the dysfunctions, hearing impairment can be explained more easily: TRPV4 is one

of the ion channels in the hair cells in the cochlea that we discussed in Chapter 5.1. So,

these ion channels are not only part of the sensation of touch, they also detect pressure

in the hair cells, and thus are part of the indirect signal transduction in hearing [12].

These ion channels are part of neurons that are part of skin (or another organ),

which means that the pressure the ion channels feels first has to be transduced through

a layer of skin. Therefore, there will always be a filtering effect by the mechanical prop-

erties of the skin or organ. The effect of the tissue has mostly been studied in animals,

and in a few cases, it has been found that the tissue can amplify the signal, instead of

the more common dampening effect that occurs [13].

Let us look at the indirect method of the mechano-sensation, which are the Merkel

cells (Figure 6.1) [14]. Merkel cells react to light touch, but they react slowly and continue

to fire with long stimulation with action potentials across their cell membrane. Their

firing pattern is irregular. There is likely a link between Merkel cells and nerve terminals

that use glutamate as their neurotransmitter. There seem to also be Merkel cells without

a connection to nerve cells; at that point, the signal might be an exocytosed chemical

diffusing into the environment. So far, though, there is no evidence of exocytosis.

Besides being a large area with different sensing neurons, skin’s other important

function is to protect against infection and injury. How does skin fulfill all of these dif-

ferent functions simultaneously? Its structure plays a key role here (Figure 6.1) [15]. The

top layer, the epidermis, is the tough protective layer. It consists of dead keratinocyte cells

that are stacked like bricks to reduce pathways for disease agents to enter the body. Ad-

ditionally, between the dead cells, there is an extra-cellular matrix (ECM), a mixture of

fibers (collagen, elastin), and amorphous matrix (proteoglycans, cell-binding adhesive

glycoproteins, solutes, water) that acts as a mechanical support and surface to anchor

cells. The ECM also determines cell orientation, controls cell growth and differentiation

via signals, and scaffolds the three-dimensional structure for optimal tissue environ-

ment and signal transport.

When an injury occurs, skin has the ability to heal itself also due to its complex

structure [15, 16]. Blood clotting is the first step in the process (Figure 6.6), a signal cas-

cade that creates a thrombus or clot. The thrombus is the initial matrix and initiates

inflammation, which starts the healing process. The matrix of the clot is reorganized

while signals recruit fibroblasts, which themselves release more signals. The reorganiz-

ing matrix also helps with building a specific structure by providing attachment points

for migrating cells. Inflammation occurs via several pathways, each of which is a sig-

nal cascade with a variety of regulation points (Table 6.2) [15, 17]. Inflammation also

initiates the innate and adaptive immune system to combat any disease-carrying bac-

teria and viruses that might have come in through the breach in the skin. Therefore,

the automatic healing system is a complex, overlapping system that is highly controlled

and adaptive to the actual injury and specific environment. Not only will blood clotting

quickly stop the bleeding, but the basic fibers will be reorganized so that cells can at-

tach to them in an organized fashion, recreating an organized tissue with blood vessels,