Although ATP-sensitive K+ (KATP) channel openers depress force, channel blockers have no effect. Furthermore, the effects of channel openers on single action potentials are quite small. These facts raise questions as to whether 1) channel openers reduce force via an activation of KATP channels or via some nonspecific effects and 2) the reduction in force by KATP channels operates by changes in amplitude and duration of the action potential. To answer the first question we tested the hypothesis that pinacidil, a channel opener, does not affect force during fatigue in muscles of Kir6.2-/- mice that have no cell membrane KATP channel activity. When wild-type extensor digitorum longus (EDL) and soleus muscles were stimulated to fatigue with one tetanus per second, pinacidil increased the rate at which force decreased, prevented a rise in resting tension, and improved force recovery. Pinacidil had none of these effects in Kir6.2-/- muscles. To answer the second question, we tested the hypothesis that the effects of KATP channels on membrane excitability are greater during action potential trains than on single action potentials, especially during metabolic stress such as fatigue. During fatigue, M wave areas of control soleus remained constant for 90 s, suggesting no change in action potential amplitude for half of the fatigue period. In the presence of pinacidil, the decrease in M wave areas became significant within 30 s, during which time the rate of fatigue also became significantly faster compared with control muscles. It is therefore concluded that, once activated, KATP channels depress force and that this depression involves a reduction in action potential amplitude.

SUMMARYCo-infection of cells with vesicular stomatitis viruses of the Indiana and New Jersey serotypes results in interference. Using specifically-labelled immunofluorescent antibodies, it was demonstrated that within any one co-infected cell, one virus serotype replicated to the relative exclusion of the other serotype. This result was further substantiated by an examination of the virus serotypes released by infectious centres co-infected with both viruses. Dominance of one serotype over the other was shown to be a function of the relative multiplicity of the two viruses. Superinfection by the second serotype at a higher multiplicity resulted in dominance by the second virus during the early period (up to I'5 h) post-infection. After this time, the minority virus was able to overcome this dominance. Dominance of the majority virus was also abolished by u.v. inactivation.Cell protein synthesis appeared to be less affected in cells infected with both serotypes than when infection was with a single serotype. INTRODUCTIONInfection of a cell culture with one virus type can, in certain circumstances, reduce the yield of a second virus type from those same cells. Examples of this heterologous interference have been studied by Marcus & Carver (I967) as well as a number of other workers (Bratt & Rubin, I968; Rott et al. I972). In contrast to the interference seen between the widely different virus groups described by these workers, interference mediated by a particular group of defective particles of vesicular stomatitis virus (VSV) is effective only against the homotypic virus strain (Huang & Wagner, I966; Crick & Brown, I973). We have previously reported that a second class of defective particles (LT particle) of the Indiana serotype of VSV can interfere not only with virus of the Indiana and closely related Cocal serotypes but can equally well interfere with the heterotypic New Jersey strain of VSV (Prevec & Kang, I97O; Prevec, t974). Heterotypic interference as mediated by LT particles does not appear to be simply a case of heterologous interference since LT particles do not interfere with two other rhabdoviruses, Piry and Chandipura (Prevec, I974).In an effort to gain some insight into the possible mechanism of heterotypic interference we re-examined the effect of co-infection of cells with non-defective (infectious) B particles of the Indiana and New Jersey serotypes. A previous study by Cooper (I958) has shown that * To whom reprint requests should be sent. Antisera and fluorescence reagents. The production and titre of the rabbit anti-NJ antiserum has been previously described (Kang & Prevec, 197o). This antiserum was conjugated with fluorescein according to the method described by Sternberger (1974). Guinea pig anti-Ind antiserum was raised in guinea pigs by 3 weekly subcutaneous injections of I ml of an equal volume of Freund's adjuvant and a suspension of ~ x ~o 9 Ind virus/ml in PBS. Two weeks after the last injection the animals were bled, and the antiserum was tested and found to be specific for Ind viru...

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