Calcium channels in excitable cell membranes.

The existence of calcium permeability in excitable cells has been appreciated for 30 years (3 I)-almost as long as we have known about voltage-depend­ ent permeabilities to sodium and potassium (46, 47). Yet, to this day, our understanding of Ca channels has lagged far behind our knowledge of Na or K channels. This situation is ironic because Ca channels are widely distributed and rival their better-characterized counterparts in diversity of biological function (42). Ca channels play a crucial role in coupling mem­ brane excitation to cellular responses such as secretion or contraction. They are primarily responsible for some specialized but very interesting forms of excitability-e.g. in the nodal regions of the heart (14, 76), the cilia of Paramecium (11, 12), or the dendrites (64) or growth cones (6) of certain neurons. Unlike Na channels, Ca channels are often modulated by hor­ mones and neurotransmitters. For many years, biophysical or biochemical analysis of Ca channels has been seriously hampered by experimental problems (e.g. 42, 81). No prepa­ ration has been as suitable and no drug as specific for Ca channels as the squid axon and tetrodotoxin are for Na channels. But the state of the art has improved recently with the development of powerful methods for recording Ca channel activity and of blocking drugs that may interact with Ca channels in a potent and specific manner. We now know that Ca channels are pores, capable of transferring millions of permeant ions per second, whose voltage-dependent properties clearly distinguish them from pumps or exchange mechanisms described elsewhere in this volume. There is growing appreciation that Ca channels can be