Читать книгу Fundamentals of Pharmacology for Paramedics - Группа авторов - Страница 31

The large, complex proteins responsible for active transport of substances across cell membranes represent another valuable drug target for manipulation of physiological function.

There are active transporters or pumps in all cell membranes for sodium, potassium and calcium ions, and these are activated when those ions have to be transported across the cell membrane against their concentration gradient, i.e. from a lower to a higher concentration of ions. Ions can move through open ion channels if they are travelling down their concentration gradient, but will need active ‘pumping’ if they are to move the other way.

Figure 1.3 Benzodiazepines act by binding to a chloride channel. (a) The inhibitory neurotransmitter GABA has its receptor on the ligand‐gated chloride ion channel in neurons. The channel also has a binding site for drugs of the benzodiazepine class. (b) Binding of GABA to its receptor opens the channel, allowing chloride ions to flow into the neuron and hyperpolarise the membrane, inhibiting further neuronal activity. (c) Binding of a benzodiazepine to its site will, in the presence of GABA, further increase the flow of chloride ions into the cell by keeping the channel open for longer, thereby further inhibiting neuronal activity.

As with enzymes and ion channels, the drugs that bind transport molecules tend to inhibit the transport when they bind. This alters cell function by interfering with the distribution of ions across the cell membrane, thereby altering membrane potential. The cardiac glycoside drug digoxin, used to treat cardiac failure, acts by binding to a transport molecule – the sodium/potassium ATP‐ase or sodium/potassium pumps on the cell membranes of cardiac muscle cells. Digoxin inhibits the function of the sodium/potassium pumps, leading to an accumulation of sodium ions inside cardiac muscle cells, which in turn results in an accumulation of calcium ions in the cells (the additional intracellular sodium ions stimulate another transporter, which pumps sodium ions out of the cell in exchange for calcium ions). The increased level of calcium ions inside the cardiac muscle cells results in stronger contractions, which translates to a stronger, more forceful heartbeat.