Abstract
Big conductance potassium (BK) channels contribute to K(+) flow and electrical behavior in many cell types. Mice made null for the gene (Kcnma1) producing the BK channel (BK(KO)) exhibit numerous deficits in physiological functions. Breeding mice lacking a single allele of Kcnma1 (C57BL/6J background) had litter sizes of approximately eight pups. For the period of maternal care (P0-P21), pup deaths peaked at P1 with a second less severe interval of death peaking near P13. Early deaths were twice as likely during a 20-month period of building construction compared with the quiescent period after cessation of construction. Births during construction were not consistent with Mendelian predictions indicating the likelihood of a specific disadvantage induced by this environmental stressor. Later BK(KO) pup deaths (~P13) also were more numerous than Mendelian expectations. After weaning, weight gain was slower for BK(KO) mice compared with wild-type littermates: 5 g less for male BK(KO) mice and 4 g less for female BK(KO) mice. Body composition determined by quantitative magnetic resonance indicated a higher fat proportion for wild-type female mice compared with males, as well as a higher hydration ratio. Both male and female BK(KO) mice showed higher fat proportions than wild-type, with female BK(KO) mice exhibiting greater variation. Together, these results indicate that BK(KO) mice suffered disadvantages that lead to prenatal and perinatal death. A metabolic difference likely related to glucose handling led to the smaller body size and distinct composition for BK(KO) mice, suggesting a diversion of energy supplies from growth to fat storage.