Two for T

Two for T Minireview other is more unexpected: a report that the already-known ␣ 1B , ␣ 1C , and ␣ 1E clones can produce single channel activity with many similarities to T-type channels Harvard Medical School Boston, Massachusetts 02115 (Meir and Dolphin, 1998). Perez-Reyes and colleagues identified the new clone by screening GenBank expressed sequence tags (ESTs) for homology to existing ␣ 1 subunits. The new channel In 1981, Lliná s and Yarom found that inferior olivary ␣ 1 subunit, named ␣1G, has relatively weak overall homol-neurons hyperpolarized from rest could generate cal-ogy to the high voltage–activated subunits but has im-cium-dependent action potentials that had even lower portant similarities in two regions likely to be crucial for thresholds than sodium action potentials. To account calcium channel function: the " P region " of each S5–S6 for this, they proposed the existence of a " low threshold " linker, believed to be important for ion permeation and calcium conductance that is largely inactivated at the selectivity, and the S4 regions thought to underlie volt-resting potential. Several years later, Carbone and Lux age-dependent gating. Mutation studies on L-type chan-(1984) made patch-clamp recordings in sensory neurons nels have shown that calcium selectivity depends on of a calcium current with exactly the properties inferred by Lliná s and Yarom: activation by small depolariza-tions, rapid inactivation, and substantial steady-state inactivation at normal resting potentials. Almost simultaneously , a number of groups studying a variety of excit-able cells, including neurons, cardiac muscle, and endo-crine cells, characterized similar channels, variously called low threshold, low voltage–activated, and T-type channels. At the single channel level, T-type channels have a lower unitary conductance (‫8ف‬ pS) than other calcium channels. At the whole-cell level, T-type currents are most obviously distinct from other calcium currents by their rapid inactivation (Figure 1A) and requirement for strongly negative holding potentials for full availability. The voltage dependence of activation of T-type current varies, and in some neurons the difference from " high voltage–activated " current is not dramatic (e.g., Figure 1C). After the recognition of distinct low voltage–activated calcium channels in neurons, attention shifted to distinctions among different high threshold calcium channels, initially made by pharmacology and single channel characteristics. Then, channel by channel, molecular cloning defined the molecular basis of calcium current. Different cloned channels have now been identified more or less certainly with components of high voltage–activated current in native cells: ␣ …