Myofibrillar regulation of contraction as revealed with phallotoxins

The thin filament regulation of striated muscle contraction involves activation of the thin filament by both Ca²⁺ and strongly bound myosin cross-bridges (XBs). Phallotoxins cause a variety of specific changes in myofibrillar functioning, being a potentially valuable tool for muscle research. There are two very distinct classes of agents among phallotoxins. One is the more recently discovered secophalloidin group. The unique property of secophalloidin is muscle activation without Ca²⁺, possibly by direct influence on actomyosin interaction. These drugs appear to be especially useful for studying the role of XBs in muscle regulation. The other is the phalloidin group, which includes the majority of phallotoxins. Binding to the phalloidin site on F-actin, they cause muscle-specific changes. In cardiac muscle they work as Ca²⁺ sensitizers, increasing both the maximal force and the Ca²⁺ sensitivity. A particular advantage of these drugs is that the target site is known, which gives an opportunity to unravel the sequence of molecular events leading to increased contractile function. The complex effect of phalloidin in skeletal muscle most probably involves disturbance of the actin-nebulin interaction, and this may help clarify the role of nebulin in regulating contraction.