Factors influencing differentiation and development of ionic channels in cardiac muscle

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Developmental changes in contractile responses of the isolated ileum of BALB/c mice treated with an antagonistic anti c-kit monoclonal antibody (ACK2) to bradykinin (BK) and acetylcholine (ACh) were examined in vitro. Isolated ileum longitudinal muscle of new-born mice (BALB/c) started to show regular rhythmic contraction 4 days after birth, but pre-treatment with ACK2 for 4 days postnatally resulted in failure of postnatal development of the regular activity of the intestine. ACH(10^<-8>M>) induced sustained contraction in a dose-dependent manner in both ACK2 treated and control ileum obtained from mice of the same age group. The sensitivity to ACh was augmented in the ACK2-treated group. The response to ACh was blocked by atropine (10^<-7>M). BK(8x10^<-11>M) produced marked contraction followed by relaxation in the ACK2-treated ileum, while in the control ileum the agent (8x10^<-9>M) induced only a small transient increase in the amplitude of spontaneous contraction. Tetrodotoxin (10^<-7>M) did not alter the response to BK in both ACK2 treated and control groups. Voltage-clamp analyses of the Ca^<2+>-dependent ionic currents in dissociated smooth muscle cells from mice treated with or without ACK2 also revealed developmental differences in both ACh and BK responses. These findings suggest that c-kit expressing cells play a crucial role in development of intracellular mechanisms for Ca^<2+> handing for contraction and relaxation in intestinal smooth muscle or in membrane sensitivity to BK and other substances.