It is estimated that the human brain contains about 1011 neurons and 1014 synaptic connections. To make matters more complex, neural circuitry is continuously sculpted in response to experience, modified as we learn and store memories, and irreversibly altered by the gradual loss of neurons and their connections as we age. How can a system so complex be subject to such change and yet continue to function stably? One emerging theory suggests that individual neurons are self-tuning devices, constantly adjusting the expression of ion channels and neurotransmitter receptors in order to maintain a stable function. How might this work?
Neurons can be categorized into functionally different types, based in part on their propensity to fire action potentials and their pattern of firing. For example, some neurons fire action potentials at high frequencies, while others fire rarely. The firing properties of each neuron type are determined to a large extent by the ion channels that the cell expresses. The number of ion channels in a neuron’s membrane is not fixed: as conditions change, a neuron can modify the numbers of depolarizing (Na+ and Ca2+) and hyperpolarizing (K+) channels and keep their proportions adjusted so as to maintain its characteristic firing behavior—a remarkable example of homeostatic control. The molecular mechanisms involved remain an important mystery.
Neuronal signals are transmitted from cell to cell at specialized sites of contact known as synapses. The usual mechanism of transmission is indirect. The cells are
Figure 11–35 Patch-clamp measurements for a single voltage-gated Na+ channel. A tiny patch of plasma membrane was detached from an embryonic rat muscle cell, as in Figure 11–34. (A) The membrane was depolarized by an abrupt shift of potential from –90 to about –40 mV. (B) Three current records from three experiments performed on the same patch of membrane. Each major current step in (B) represents the opening and closing of a single channel. A comparison of the three records shows that, whereas the durations of channel opening and closing vary greatly, the rate at which current flows through an open channel (its conductance) is practically constant. The minor fluctuations in the current records arise largely from electrical noise in the recording apparatus. Current flowing into the cell, measured in picoamperes (pA), is shown as a downward deflection of the curve. By convention, the electrical potential on the outside of the cell is defined as zero.
(C) The sum of the currents measured in 144 repetitions of the same experiment. This aggregate current is equivalent to the usual Na+ current that would be observed flowing through a relatively large region of membrane containing 144 channels. A comparison of (B) and (C) reveals that the time course of the aggregate current reflects the probability that any individual channel will be in the open state; this probability decreases with time as the channels in the depolarized membrane adopt their inactivated conformation. (Data from J. Patlak and R. Horn,  J. Gen. Physiol. 79:333–351, 1982. With permission from The Rockefeller University Press.) nerve terminal of presynaptic cell neurotransmitter in synaptic vesicle