The ability of mechanically skinned muscle fibres from the rat to respond to T-system depolarisation was studied in relation to muscle glycogen content. Muscle glycogen was altered by incubating extensor digitorum longus (EDL) muscles in Krebs solution without glucose or in Krebs solution with glucose (10 mM) and insulin (20 U.l-1). The glycogen content of muscles stored without glucose was rather stable between 30 and 480 min (11.27 +/- 0.39 mumol.g-1), while the muscles stored with glucose and insulin maintained an elevated and stable level of glycogen (23.48 +/- 1.67 mumol.g-1) between 100 and 360 min. Single mechanically skinned fibres from paired muscles, incubated in either glucose-free Krebs or in Krebs with glucose and insulin, were subjected to cycles of T-system depolarisation-repolarisation in a controlled environment (8 mM ATP, 10 mM creatine phosphate, 1 mM Mg2+, pH 7.10) and the force response was monitored until the force had declined to 50% of the maximum response (50% rundown). Fibres from muscles with a higher glycogen content reached 50% rundown after a larger number of depolarisations and displayed consistently larger average response capacity values, calculated as the sum of the force responses to 50% rundown divided by the maximum Ca(2+)-activated force response in that fibre. Thus skinned fibres originating from muscles with a higher glycogen content have an increased ability to respond to T-system depolarisation when the effect of metabolite accumulation is minimised and the function of glycogen acting as an energy source is by-passed. This provides direct support to the hypothesis that glycogen has a protective role in maintaining fibre excitability.

Contractile activation properties of intact and chemically skinned ventricular myocardium preparations were studied in juvenile (3-4 weeks old), adult euthyroid and adult hypothyroid rats. The rats were made hyperthyroid by treatment with iodine-131 and propylthiouracil. The ventricular muscle of euthyroid rats contains a mixture of isozymes of myosin while the myocardium of juvenile and hypothyroid rats are relatively pure in regard to V1 and V3 types of myosin respectively. No significant differences were found in either the maximum Ca2+ activated or rigor force developed by "chemically skinned" preparations in either the juvenile or hypothyroid groups compared with euthyroid adults, suggesting that there is no difference between myocardia with different isozymes of myosin in the intrinsic capacity to generate force. In the hypothyroid (V3) preparations there was a significant shift in the force/pCa relation to the left compared with the euthyroid adult (mixture of V1 and V3 isozymes). The force/pCa relation for the juvenile lay in between that for the hypothyroid and euthyroid adults. The greater apparent Ca2+ sensitivity to activation in the hypothyroid group may relate to a slower cross-bridge cycling rate or altered Ca2+ kinetics in ventricular myocardium with exclusively V3 isozyme. In intact papillary muscles differences were found in the dependence of force on extracellular [Ca2+] such that a higher extracellular [Ca2+] was required for muscles from hypothyroid animals to attain maximum twitch force than those from juveniles. The force/frequency relations also differed, with the hypothyroid group being better able to sustain force as stimulation frequency increased than the juvenile group.(ABSTRACT TRUNCATED AT 250 WORDS)

Aim: Dantrolene interacts with ryanodine receptors in skeletal and cardiac muscle affecting sarcoplasmic reticulum calcium release. Since dantrolene is lipophilic it could also affect intra-sarcoplasmic reticulum calcium handling proteins such as calsequestrin. This study investigated whether dantrolene (1-30 µmol/L) alters the polymerization state and the calcium binding capacity of recombinant cardiac calsequestrin and cardiac sarcoplasmic reticulum calcium handling. Methods: Human recombinant cardiac calsequestrin was used to make simultaneous measurements of turbidity (to indicate calsequestrin polymerization) and calcium binding to calsequestrin in the presence and absence of dantrolene.Caffeine-induced Ca 2+ transients were used to investigate the effects of dantrolene on sarcoplasmic reticulum calcium loading and release in saponin-permeabilized cardiomyocytes laid down in monolayers in 96-well array plates. Results: Dantrolene (1-30 µmol/L) increased the polymerization state of calsequestrin and its calcium binding capacity. In the presence of dantrolene, calsequestrin-dependent turbidity increased 2.5-11.5-fold at 1.0 mmol/L calcium added to unbuffered Ca 2+ solutions and 3-10-fold when calcium was raised from 0.06 to 30 µmol/L. The dantrolene-dependent increase in turbidity at 30 µmol/L dantrolene was associated with a 3-fold increase in the number of calcium ions bound per calsequestrin molecule at 30 and 100 µmol/L calcium. The caffeine-induced releasable calcium loaded by the sarcoplasmic reticulum at 0.63 µmol/L free calcium in permeabilized cardiomyocytes was also increased in the presence of 30 µmol/L dantrolene. Conclusion: Dantrolene alters the polymerization state and the calcium binding properties of cardiac calsequestrin and increases sarcoplasmic reticulum calcium loading in permeabilized cardiomyocytes.

No abstract

Background: Men are notorious for not attending to their health and seeking health advice, especially in rural areas. Aim: To ascertain the role community pharmacists can play in men's health in rural Victoria. Method: Self-administered, closed-response written questionnaires were sent to community pharmacists and men in the Loddon-Mallee region of Victoria. Results: The men and pharmacists agreed that community pharmacies could be a useful men's health resource. Half the men thought that the only advice pharmacists gave concerned prescription medications. Men said that the gender of a pharmacist would not affect them seeking advice, yet among their criteria for making pharmacies more 'men friendly' was the provision of more male pharmacists and pharmacy assistants. Both men and pharmacists saw information leaflets as a valuable resource. The men and pharmacists agreed that the service to men could be improved with provision of more information, counselling, education sessions, referral and collaboration with other health professionals, men's health events and some risk factor screening. Pharmacists were confident and reported success in counselling men in some areas (e.g. smoking cessation) but not others (e.g. alcohol use). Some constraints to improving pharmacy services to men were identified including time constraints, lack of remuneration and training. Conclusion: Rural pharmacies could become a useful men's health resource. Time, lack of remuneration and training may be the main constraints.