The stimulated region undergoes a rapid change of electrical potential, becoming externally negative relatively to its resting condition; the neighboring still inactive regions being thus positive relatively to the active region, the conditions for the flow of an electrical current between stimulated and unstimulated regions arise. This current is undoubtedly of sufficient strength to stimulate the tissue for some distance beyond the immediate site of stimulation. The voltage of the action-current of frog's nerve is at least thirty millivolts; and a current between platinum electrodes two or three centimeters apart differing in potential by this degree is amply sufficient to stimulate an irritable nerve. The conditions when the two regions of different potential are not externally applied electrodes but portions of the nerve itself are not essentially different; in either case a current flows along the nerve; and if this current is intense enough and arises suddenly enough it must stimulate the latter. There is thus reason to believe that the electrical variation accompanying stimulation is the main condition of propagation of the excited state. This conclusion is supported by various experimental facts; for instance, it is found that the rate of development of the electric variation and the rate of passage of the impulse are influenced to the same degree by changes of temperature, and by certain chemical substances such as the anesthetics. There are various other facts pointing in the same direction, and there are also certain difficulties in the way of this conception; but into these we cannot enter here. The fact remains that the electrical variation is the only known peculiarity of the local process that can account for its self-propagating character; and recent determinations.of the minimal current needed for excitation indicate that the bioelectric currents are of sufficient intensity to serve as the basis for this propagation.
It is clear that propagation of the state of excitation from the immediate site of stimulus over the entire cell or nerve fibre is indispensable to stimulation of any irritable element as a whole by any local stimulus; so that if the above view is correct we must regard the electrical variation as perhaps the most essential feature of the stimulation process. If so, we can understand why the electrical current has such universal stimulating action. In passing a current through a tissue we are artifically setting up differences of electrical potential between different portions of the irritable elements, and according to the above conception this should always cause excitation if the current is strong enough and rises to its maximum with sufficient rapidity. That this is in fact the case needs no emphasis. The electrical current is recognized as the most universal form of stimulus; and all irritable cells and elements, virtually without exception, respond to its action.
We conclude then that the critical or initiatory event in stimulation is an electrical change, consisting essentially in a sudden decrease in the electrical potential of the external surface of the irritable element at the
