Study on the genetic mechanism underlying "hypocalcemic myopathy" using an animal model

(1)Rats were pair-fed either a control or a Ca-and vitamin D I D23 ii D2-deficient diet after weaning(3weeks Of Age)。Hypocalcemia was confirmed in the deficient diet-fed rats(Termed E)；plasma Ca and Ca ion concentrations were about half in those of control rats(Termed C)。These values were consistent with our previous results.Plasma Mg was analyzed as well，to confirm no contribution to hypocalcemic myopathy.(2)The membrane potential was measured in soleus(SOL：slow twitch muscle)and extensor digitorum longus(EDL：fast twitch muscle)muscles isolated from E and C rats.Electrical measurement was performed using a conventional glass microelectrode method in Tyrode solutions containing low Ca(termed Lo，0.45 mM)or high Ca(termed Hi，1.12 mM)。The resting membrane potential obtained from SOL or EDL in hypocalcemic rats(E-Lo)did not significantly differ from that in control rats(C-Hi)。Parameters of the action potential in SOL differed significantly from E-Lo(n=21)to C-Hi(n=28)：amplitude(mean±SD；E-Lo/C-Hi)：66±5.0/77±9.4 mV(p&lt；0.0001)，half duration：3.0±0.7/2.5±0.6ms(p&lt；0.01)，Vmax：62±36/84±25v/s(p&lt；0.005)，-Vmax：-25±9/-35±12v/s(p&lt；0.005)。On the other hand，each parameter of the action potential from EDL muscle was similar between E-Lo(n=19)and C-Hi(n=1)(p&gt；0.05).These results suggest that the hypocalcemia-induced increase in serum CK may be attributable to membrane modification of slow twitch muscles.

(1) Rats were pair-fed either a control or a Ca- and vitamin DィイD23ィエD2-deficient diet after weaning (3 weeks of age). Hypocalcemia was confirmed in the deficient diet-fed rats (termed E) ; plasma Ca and Ca ion concentrations were about half in those of control rats (termed C). These values were consistent with our previous results. Plasma Mg was analyzed as well, to confirm no contribution to hypocalcemic myopathy.(2) The membrane potential was measured in soleus (SOL : slow twitch muscle) and extensor digitorum longus (EDL : fast twitch muscle) muscles isolated from E and C rats. Electrical measurement was performed using a conventional glass microelectrode method in Tyrode solutions containing low Ca (termed Lo, 0.45 mM) or high Ca (termed Hi, 1.12 mM). The resting membrane potential obtained from SOL or EDL in hypocalcemic rats (E-Lo) did not significantly differ from that in control rats (C-Hi). Parameters of the action potential in SOL differed significantly from E-Lo (n=21) to C-Hi (n=28) : amplitude (mean±SD ; E-Lo/C-Hi) : 66±5.0/77±9.4 mV (p<0.0001), half duration : 3.0±0.7/2.5±0.6 ms (p<0.01), Vmax : 62±36/84±25 v/s (p<0.005), -Vmax : -25±9/-35±12 v/s (p<0.005). On the other hand, each parameter of the action potential from EDL muscle was similar between E-Lo (n=19) and C-Hi (n=1) (p>0.05).These results suggest that the hypocalcemia-induced increase in serum CK may be attributable to membrane modification of slow twitch muscles.