For those ion channel biophysicists who are also in the signal transduction business, it can sometimes seem like a marriage of strange bedfellows. In the world of voltage gating and permeation studies the analysis is usually meticulously precise and the results often presented using dense mathematics. Gating charges are calculated to the last e, molecular movements debated to the last Å, and state occupancies may be many decimal places in length. However, when we turn to regulation of the channels, we usually become less demanding. When we say that a drug or an analogue blocks a certain signal, we usually do not mean that the signal actually was eliminated, but rather that it was reduced. It can be a messy business, but this messiness is brought on, not by the languor of the investigator, but by the imperfect nature of many of the...

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